PubMed

Pestic Biochem Physiol. 2023 Sep;195:105580. doi: 10.1016/j.pestbp.2023.105580. Epub 2023 Aug 11.ABSTRACTRed swamp crayfish, Procambarus clarkii, is a globally invasive species, which has caused great damage to biodiversity, agriculture, and fishing. Therefore, the development of effective management methods, such as pheromone control, is necessary for biological control and biodiversity protection. However, the components of P. clarkii sex pheromones have not yet been explored, and the chemosensory mechanism of the P. clarkii antennae after stimulation by sex pheromone also remains unknown. In this study, we isolated and identified the candidate bioactive component of the female P. clarkii sex pheromone using ultrafiltration centrifugation, semi-preparative liquid phase separation and omics technologies and conducted bioassays to determine its attraction ability. Meanwhile, RNA-Seq technology was used to analyze the potential chemosensory mechanism of antennae. Our results indicated that the male P. clarkii were uniaxially attracted to the female crude conditioned water (FCW), medium fraction (MF, isolated by ultrafiltration centrifugation), and preparative fragment 6 of females (PFF6, isolated by semi-preparative liquid phase separation). Metabolomic analysis revealed the presence of 18 differential metabolites between the PFF6 and PFM6 samples, among which 15 were significantly upregulated in the PFF6 sample. Bioassay test also showed that mestranol, especially at concentrations of 10-5-10-2 mol∙l-1, could significantly attract P. clarkii males; therefore, mestranol was identified as the candidate sex pheromone component of P. clarkii females. Furthermore, RNA-Seq results showed that most differentially expressed genes (DEGs) enriched in lipid metabolism and signal transduction pathways were up-regulated in P. clarkii males. In addition, high expressions of Ca2+-binding protein and ion transporting ATPases may enhance the sensitivity of the antennae of P. clarkii males towards sex pheromones. Our study provides data on P. clarkii sex pheromone composition and reveals the molecular mechanism of sex pheromone response in P. clarkii. Moreover, our study provides a referable method for the isolation of candidate bioactive molecules from the P. clarkii sex pheromone.PMID:37666605 | DOI:10.1016/j.pestbp.2023.105580

Pestic Biochem Physiol. 2023 Sep;195:105525. doi: 10.1016/j.pestbp.2023.105525. Epub 2023 Jul 11.ABSTRACTPlant pathogens can develop multidrug resistance (MDR) through metabolomic and efflux activities. Although MDR has been observed in the field, its mechanisms are yet to be further studied. MDR in Rhizoctonia solani induced by the uncoupler SYP-14288, which involved efflux transporters including ATP binding cassette (ABC) and major facilitator superfamily (MFS) have been reported in our previous study. To confirm this, corresponding genes of the wild-type R. solani X19 and its derived MDR mutant X19-7 were compared through transcriptomics, RNA-Seq data validation, and heterologous expression. Genes encoding six ABC transporters and seven MFS transporters were identified to be associated with MDR and mostly showed a constitutively higher expression in X19-7 than in X19 regardless of SYP-14288 treatment. Eight ABC transporter-encoding genes and eight MFS transporter-encoding genes were further characterized by transferring into Saccharomyces cerevisiae. The sensitivity of transformants containing either ABC transporter-encoding gene AG1IA_06082 and MFS transporter-encoding gene AG1IA_08645 was significantly decreased in responses to fungicides having various modes of action including SYP-14288, fluazinam, chlorothalonil, and difenoconazole, indicating that these two genes were related to MDR. The roles of two genes were further confirmed by successfully detecting their protein products and high accumulation of SYP-14288 in yeast transformants. Thus, ABC and MFS transporters contributed to the development of MDR in R. solani. The result helps to understand the cause and mechanisms that influence the efficient use of fungicide.PMID:37666584 | DOI:10.1016/j.pestbp.2023.105525

Sci Total Environ. 2023 Sep 2:166795. doi: 10.1016/j.scitotenv.2023.166795. Online ahead of print.ABSTRACTShort-term exposure to ozone (O3) has been associated with airway inflammation. Given that high temperature (HT) accelerates O3 production, it is of significance to determine whether co-exposure to HT exacerbates O3-induced airway inflammation. The aim of this study was to examine the possible promotive effect of HT on O3-induced airway inflammation and underlying mechanisms. Forty-eight C57BL/6 N male mice were randomly divided into four groups: filtered air (control), O3, HT, and HT + O3 (co-exposure) groups. Mice in control and O3 groups were exposed to filtered air or 1 ppm O3 at 24 °C, respectively, while mice in HT and co-exposure groups were exposed to filtered air or 1 ppm O3 at 36 °C, respectively. The exposure scenario for four groups was 4 h/d for 5 consecutive days. Bronchoalveolar lavage fluids (BALF) were collected 24 h after the last exposure and subjected to examinations of oxidative stress and inflammation biomarkers, 16S rRNA sequencing, and metabolic profiling. Lung tissues were processed for H&E histological staining. The results showed that O3 inhalation triggered oxidative stress and inflammation in the airways, which was worsen by co-exposure to HT. Further studies revealed that co-exposure to HT strengthened O3-induced decline in Firmicutes and Allobaculum in airways. Moreover, co-exposure to HT promoted O3-induced airway metabolic disorder. Spearman correlation analysis revealed correlations among microbiota dysbiosis, metabolic disorder, oxidative stress and inflammation induced by co-exposure to HT and O3. Taken together, HT exposure aggravates O3-induced airway oxidative stress and inflammation, possibly through modulation of microbiota and metabolism of the airways.PMID:37666337 | DOI:10.1016/j.scitotenv.2023.166795

Food Chem Toxicol. 2023 Sep 2:114012. doi: 10.1016/j.fct.2023.114012. Online ahead of print.ABSTRACTIn order to investigate the amelioration of docosahexaenoic acid-enriched phosphatidylserine (DHA-PS) on bisphenol A (BPA)-induced nephrotoxicity, the murine nephrotoxicity model was established by intragastric administration of BPA (5 mg/kg/B.W.) for 6 weeks. The biochemical indices, hematoxylin-eosin (H&E) staining, kidney metabolomics, and related protein expression levels of SIRT1-AMPK pathway were then determined. Our results indicated that DHA-PS (100 mg/kg/B.W.) ameliorated the BPA-induced nephrotoxicity after 6 weeks of intragastric administration, primarily by decreasing the serum creatinine (CRE) and blood urea nitrogen (BUN), renal inflammatory cytokines and lipid levels, and increasing the antioxidant enzyme activities. In addition, the untargeted metabolomics of the kidney indicated that BPA perturbed the tryptophan metabolism, pyridine metabolism, and valine, leucine, and isoleucine biosynthesis, while DHA-PS administration significantly affected the glycerophospholipid metabolism, valine, leucine, and isoleucine biosynthesis to ameliorate the BPA-induced metabolic disorder. Moreover, DHA-PS administration could ameliorate the BPA-induced lipid disturbance by upregulating the expressions of AMPKα1, SIRT1, and PPARα while downregulating the expression of SREBP-1c through the SIRT1-AMPK pathway. This is the first time that the amelioration effects of DHA-PS on BPA-induced nephrotoxicity have been investigated from multiple perspectives, suggesting that DHA-PS might be a potential dietary supplement for reducing BPA-induced nephrotoxicity.PMID:37666289 | DOI:10.1016/j.fct.2023.114012

Int Immunopharmacol. 2023 Sep 2;124(Pt A):110883. doi: 10.1016/j.intimp.2023.110883. Online ahead of print.ABSTRACTDiabetes accelerates muscle atrophy, leading to the deterioration of skeletal muscles. This study aimed to assess the potential of the β2-adrenoceptor agonist, salbutamol (SLB), to alleviate muscle atrophy in streptozotocin (STZ)-induced diabetic rats. Male Sprague Dawley rats were randomized into four groups (n=6): control, SLB, STZ (55 mg/kg, single i.p.), and STZ + SLB (6 mg/kg, orally for 4 weeks). After the final SLB dose, animals underwent tests to evaluate muscle strength and coordination, including forelimb grip strength, wire-hanging, actophotometer, rotarod, and footprint assessments. Rats were then sacrificed, and serum and gastrocnemius (GN) muscles were collected for further analysis. Serum evaluations included proinflammatory markers (tumor necrosis factor α, interleukin-1β, interleukin-6), muscle markers (creatine kinase, myostatin), testosterone, and lipidemic markers. Muscle oxidative stress (malonaldehyde, protein carbonyl), antioxidants (glutathione, catalase, superoxide dismutase), and histology were also performed. Additionally, 1H nuclear magnetic resonance serum profiling was conducted. SLB notably enhanced muscle grip strength, coordination, and antioxidant levels, while reduced proinflammatory markers and oxidative stress in STZ-induced diabetic rats. Reduced serum muscle biomarkers, increased testosterone, restored lipidemic levels, and improved muscle cellular architecture indicated SLB's positive effect on muscle condition in diabetic rats. Metabolomics profiling revealed that the STZ group significantly increased the phenylalanine-to-tyrosine ratio (PTR), lactate-to-pyruvate ratio (LPR), acetate, succinate, isobutyrate, and histidine. SLB administration restored these perturbed serum metabolites in the STZ-induced diabetic group. In conclusion, salbutamol significantly protected against skeletal muscle wasting in STZ-induced diabetic rats.PMID:37666067 | DOI:10.1016/j.intimp.2023.110883

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2023 Aug 20;41(8):569-575. doi: 10.3760/cma.j.cn121094-20221124-00558.ABSTRACTObjective: To screen the differential metabolites and metabolic pathways in silicosis model by analyzing plasma metabolomics of silicosis rats. Methods: In May 2021, twenty male SD rats were randomly divided into control group (C), 1-week silicosis group (S1W), 2-week silicosis group (S2W) and 4-week silicosis group (S4W), with 5 rats in each group. Rats were intratracheally instillated with 1ml crystalline SiO(2) suspension (50 mg/ml) or normal saline and were sacrificed after 1 week, 2 weeks and 4 weeks, HE staining was used to observe the lung pathology of rats. The plasma samples were analyzed by UPLC-IMS-QTOF mass spectrometer to screen out potential differential metabolites in silicosis models and analyze their lipid enrichment. Results: HE results showed that nodules formed in the silicosis model group, and with the extension of time, nodules gradually increased and alveolar structure was gradually destroyed. Metabolomics screened out 14 differential metabolites in S1W, 24 in S2W, and 28 in S4W, and found that the differential metabolites were mainly enriched in the metabolism of glycerophospholipid metabolism, fatty acid degradation, Glycosylphosphatidylinositol (GPI) -anchor biosynthesis, fatty acid elongation and other metabolic pathways. Conclusion: There are significant changes in plasma lipid metabolites in silicosis rat models.PMID:37667151 | DOI:10.3760/cma.j.cn121094-20221124-00558

Nat Biotechnol. 2023 Sep 4. doi: 10.1038/s41587-023-01937-y. Online ahead of print.ABSTRACTWe present a spatial omics approach that combines histology, mass spectrometry imaging and spatial transcriptomics to facilitate precise measurements of mRNA transcripts and low-molecular-weight metabolites across tissue regions. The workflow is compatible with commercially available Visium glass slides. We demonstrate the potential of our method using mouse and human brain samples in the context of dopamine and Parkinson's disease.PMID:37667091 | DOI:10.1038/s41587-023-01937-y

Commun Biol. 2023 Sep 4;6(1):906. doi: 10.1038/s42003-023-05271-6.ABSTRACTSubnival glasshouse plants provide a text-book example of high-altitude adaptation with reproductive organs enclosed in specialized semi-translucent bracts, monocarpic reproduction and continuous survival under stress. Here, we present genomic, transcriptomic and metabolomic analyses for one such plant, the Noble rhubarb (Rheum nobile). Comparative genomic analyses show that an expanded number of genes and retained genes from two recent whole-genome duplication events are both relevant to subnival adaptation of this species. Most photosynthesis genes are downregulated within bracts compared to within leaves, and indeed bracts exhibit a sharp reduction in photosynthetic pigments, indicating that the bracts no longer perform photosynthesis. Contrastingly, genes related to flavonol synthesis are upregulated, providing enhanced defense against UV irradiation damage. Additionally, anatomically abnormal mesophyll combined with the downregulation of genes related to mesophyll differentiation in bracts illustrates the innovation and specification of the glass-like bracts. We further detect substantial accumulation of antifreeze proteins (e.g. AFPs, LEAs) and various metabolites (e.g. Proline, Protective sugars, procyanidins) in over-wintering roots. These findings provide new insights into subnival adaptation and the evolution of glasshouse alpine plants.PMID:37667004 | DOI:10.1038/s42003-023-05271-6

Magn Reson Chem. 2023 Sep 4. doi: 10.1002/mrc.5392. Online ahead of print.ABSTRACTOne-dimensional (1D) proton-nuclear magnetic resonance (1 H-NMR) spectroscopy is an established technique for the deconvolution of complex biological sample types via the identification/quantification of small molecules. It is highly reproducible and could be easily automated for small to large-scale bioanalytical, epidemiological, and in general metabolomics studies. However, chemical shift variability is a serious issue that must still be solved in order to fully automate metabolite identification. Herein, we demonstrate a strategy to increase the confidence in assignments and effectively predict the chemical shifts of various NMR signals based upon the simplest form of statistical models (i.e., linear regression). To build these models, we were guided by chemical homology in serum/plasma metabolites classes (i.e., amino acids and carboxylic acids) and similarity between chemical groups such as methyl protons. Our models, built on 940 serum samples and validated in an independent cohort of 1,052 plasma-EDTA spectra, were able to successfully predict the 1 H NMR chemical shifts of 15 metabolites within ~1.5 linewidths (Δv1/2 ) error range on average. This pilot study demonstrates the potential of developing an algorithm for the accurate assignment of 1 H NMR chemical shifts based solely on chemically defined constraints.PMID:37666776 | DOI:10.1002/mrc.5392

Sci Bull (Beijing). 2023 Aug 28:S2095-9273(23)00587-X. doi: 10.1016/j.scib.2023.08.047. Online ahead of print.ABSTRACTMetabolomics is a nascent field of inquiry that emerged in the late 20th century. It encompasses the comprehensive profiling of metabolites across a spectrum of organisms, ranging from bacteria and cells to tissues. The rapid evolution of analytical methods and data analysis has greatly accelerated progress in this dynamic discipline over recent decades. Sophisticated techniques such as liquid chromatograph mass spectrometry (MS), gas chromatograph MS, capillary electrophoresis MS, and nuclear magnetic resonance serve as the cornerstone of metabolomic analysis. Building upon these methods, a plethora of modifications and combinations have emerged to propel the advancement of metabolomics. Despite this progress, scrutinizing metabolism at the single-cell or single-organelle level remains an arduous task over the decades. Some of the most thrilling advancements, such as single-cell and single-organelle metabolic profiling techniques, offer profound insights into the intricate mechanisms within cells and organelles. This allows for a comprehensive study of metabolic heterogeneity and its pivotal role in multiple biological processes. The progress made in MS imaging has enabled high-resolution in situ metabolic profiling of tissue sections and even individual cells. Spatial reconstruction techniques enable the direct representation of metabolic distribution and alteration in three-dimensional space. The application of novel metabolomic techniques has led to significant breakthroughs in biological and clinical studies, including the discovery of novel metabolic pathways, determination of cell fate in differentiation, anti-aging intervention through modulating metabolism, metabolomics-based clinicopathologic analysis, and surgical decision-making based on on-site intraoperative metabolic analysis. This review presents a comprehensive overview of both conventional and innovative metabolomic techniques, highlighting their applications in groundbreaking biological and clinical studies.PMID:37666722 | DOI:10.1016/j.scib.2023.08.047

Mycotoxin Res. 2023 Sep 4. doi: 10.1007/s12550-023-00502-5. Online ahead of print.ABSTRACTAfter India and the USA, Pakistan is the third country leading in global dairy production, a sector of very high socioeconomic relevance in Asia. Mycotoxins can affect animal health, reproduction and productivity. This study analysed a broad range of co-occurring mycotoxins and fungal secondary metabolites derived from Alternaria, Aspergillus, Fusarium, Penicillium and other fungal species. To complete this, a validated multi-metabolite liquid chromatography/electrospray ionization-tandem mass spectrometric (LC/ESI-MS/MS) method was employed, detecting 96 of > 500 tested secondary fungal metabolites. This first preliminary study demonstrated that total mixed rations (TMRs) (n = 30) from big commercial dairy cattle farms (> 200 lactating cows) in Punjab, Pakistan, presented ubiquitous contamination with mixtures of mycotoxins. The mean of mycotoxins per sample was 14, ranging from 11 to 20 mycotoxins among all TMR samples. Metabolites derived from other fungi and Fusarium spp. showed the highest levels, frequency and diversity among the detected fungal compounds. Among the most prevalent mycotoxins were Fusarium toxins like fumonisins B1 (FB1) (93%), B2 (FB2) (100%) and B3 (FB3) (77%) and others. Aflatoxin B1 (AFB1) was evidenced in 40% of the samples, and 7% exceeded the EU maximum limit for feeding dairy cattle (5 µg/kg at 88% dry matter). No other mycotoxin exceeds the EU guidance values (GVs). Additionally, we found that dietary ingredients like corn grain, soybean meal and canola meal were related to increased contamination of some mycotoxins (like FB1, FB2 and FB3) in TMR from the province of Punjab, Pakistan. Among typical forage sources, the content of maize silage was ubiquitous. Individually, the detected mycotoxins represented relatively low levels. However, under a realistic scenario, long-term exposure to multiple mycotoxins and other fungal secondary metabolites can exert unpredictable effects on animal health, reproduction and productivity. Except for ergot alkaloids (73%), all the groups of metabolites (i.e. derived from Alternaria spp., Aspergillus spp., Fusarium spp., Penicillium spp. and other fungi) occurred in 100% of the TMR samples. At individual levels, no other mycotoxins than AFB1 represented a considerable risk; however, the high levels of co-occurrence with several mycotoxins/metabolites suggest that long-term exposure should be considered because of their potential toxicological interactions (additive or synergistic effects).PMID:37665547 | DOI:10.1007/s12550-023-00502-5

Fish Physiol Biochem. 2023 Sep 4. doi: 10.1007/s10695-023-01234-0. Online ahead of print.ABSTRACTThe study investigated the alleviated effects of Alpha-ketoglutaric acid (AKG) on the intestinal health of mirror carp (Cyprinus carpio Songpu) caused by soy antigenic protein. The diets were formulated from fishmeal (CON), 50% soybean meal (SBM), the mixture of glycinin and β-conglycinin (11 + 7S) and adding 1% AKG in the 11 + 7S (AKG). Carp (~ 4 g) in triplicate (30 fish per tank) was fed to apparent satiation thrice a day for six weeks. Compared with CON, SBM treatment resulted in significantly poor growth performance (P < 0.05), whereas 11 + 7S and AKG treatments were not significantly different from CON (P > 0.05). Gene expression of tumor necrosis factor (TNF-α) and interleukin-1 β (IL-1β) in proximal intestines (PI) and distal intestines (DI) were increased (P < 0.05), and transforming growth factor (TGF-β) in PI and middle intestines (MI) was decreased (P < 0.05) in both SBM and 11 + 7S. The caspase-3 in DI increased in SBM (P < 0.05) and the caspase-3 and caspase-9 in DI increased in 11 + 7S (P < 0.05); conversely, TGF-β in PI and MI was increased, TNF-α and IL-1β in the MI, caspase-3, and caspase-9 in DI was decreased in AKG (P < 0.05). The TOR (target of rapamycin) in PI and MI, ACC in PI, MI and DI was decreased in SBM (P < 0.05), the AMPK in the PI and DI, TOR in PI, MI and DI, ACC in PI and DI, 4E-BP in DI was reduced in 11 + 7S (P < 0.05). AMPK in the PI and DI, ACC in the PI and MI, TOR in PI, MI, and DI, 4E-BP in PI and DI was recovered by AKG supplementation (P < 0.05). Lipids and lipid-like metabolism, organic acids and derivatives metabolism increased in AKG dietary treatment. In conclusion, AKG reduces the expression of intestinal inflammation and apoptosis pathway and changes glycerophospholipid metabolism and sphingolipid metabolism in the intestine of fish.PMID:37665506 | DOI:10.1007/s10695-023-01234-0

Arch Toxicol. 2023 Sep 4. doi: 10.1007/s00204-023-03572-7. Online ahead of print.ABSTRACTOmics techniques have been increasingly recognized as promising tools for Next Generation Risk Assessment. Targeted metabolomics offer the advantage of providing readily interpretable mechanistic information about perturbed biological pathways. In this study, a high-throughput LC-MS/MS-based broad targeted metabolomics system was applied to study nitrofurantoin metabolic dynamics over time and concentration and to provide a mechanistic-anchored approach for point of departure (PoD) derivation. Upon nitrofurantoin exposure at five concentrations (7.5 µM, 15 µM, 20 µM, 30 µM and 120 µM) and four time points (3, 6, 24 and 48 h), the intracellular metabolome of HepG2 cells was evaluated. In total, 256 uniquely identified metabolites were measured, annotated, and allocated in 13 different metabolite classes. Principal component analysis (PCA) and univariate statistical analysis showed clear metabolome-based time and concentration effects. Mechanistic information evidenced the differential activation of cellular pathways indicative of early adaptive and hepatotoxic response. At low concentrations, effects were seen mainly in the energy and lipid metabolism, in the mid concentration range, the activation of the antioxidant cellular response was evidenced by increased levels of glutathione (GSH) and metabolites from the de novo GSH synthesis pathway. At the highest concentrations, the depletion of GSH, together with alternations reflective of mitochondrial impairments, were indicative of a hepatotoxic response. Finally, a metabolomics-based PoD was derived by multivariate PCA using the whole set of measured metabolites. This approach allows using the entire dataset and derive PoD that can be mechanistically anchored to established key events. Our results show the suitability of high throughput targeted metabolomics to investigate mechanisms of hepatoxicity and derive point of departures that can be linked to existing adverse outcome pathways and contribute to the development of new ones.PMID:37665362 | DOI:10.1007/s00204-023-03572-7

Environ Toxicol. 2023 Sep 4. doi: 10.1002/tox.23942. Online ahead of print.ABSTRACTEmamectin benzoate (EMB) is an insecticide for the control of agricultural lepidoptera pests, and also an anti-parasiticide for the control of exoparasites in aquaculture industry. Increased studies suggest that EMB could cause toxicity to non-targeted organisms, but its immunotoxicity to human remains unclear. In this study, zebrafish were used to investigate the immunotoxic effects induced by environmentally relevant doses of EMB. We observed that EMB exposure led to embryo mortality and delayed hatching, as well as increased malformations. Meanwhile, zebrafish exposed to EMB exhibited a significant decrease in the number of neutrophils and macrophages. In addition, untargeted metabolomics approach was developed to elucidate the mechanism of EMB-induced immunotoxicity. We found that a total of 10 shared biomarkers were identified in response to EMB exposure. Furthermore, pathway analysis identified glycerophospholipid metabolism was the most relevant pathway. Within this pathway, it was observed abnormal increases in glycerol 3-phosphate content, which could be attributed to the increased expression of GK5 and decreased expression of GPAT3. Our study provided novel and robust perspectives, which showed that EMB exposure to zebrafish embryos could cause metabolic disturbances that adversely affected development and immune system.PMID:37665110 | DOI:10.1002/tox.23942

Food Funct. 2023 Sep 4. doi: 10.1039/d2fo03988e. Online ahead of print.ABSTRACTIt is well-established that consumption of cruciferous and brassica vegetables has a correlation with reduced rates of many negative health outcomes. There is an increased interest in identifying food intake biomarkers to address limitations related to self-reported dietary assessment. The study aims to identify biomarkers of broccoli intake using metabolomic approaches, examine the dose-response relationship, and predict the intake by multimarker panel. Eighteen volunteers consumed cooked broccoli in A-Diet Discovery study and fasting and postprandial urine samples were collected at 2, 4 and 24 hours. Subsequently the A-Diet Dose-response study was performed where volunteers consumed different portions of broccoli (49, 101 or 153 g) and urine samples were collected at the end of each intervention week. Urine samples were analysed by 1H-NMR and LC-MS. Multivariate data analysis and one-way ANOVA were performed to identify discriminating biomarkers. A panel of putative biomarkers was examined for its ability to predict intake through a multiMarker model. Multivariate analysis revealed discriminatory spectral regions between fasting and fed metabolic profiles. Subsequent time-series plots revealed multiple features increased in concentration following the consumption. Urinary S-methyl cysteine sulfoxide (SMCSO) increased as broccoli intake increased (0.17-0.24 μM per mOSM per kg, p < 0.001). Similarly from LC-MS data genipin, dihydro-β-tubaic acid and sinapic acid increased with increasing portions of intake. A panel of 8 features displayed good ability to predict intake from biomarker data only. In conclusion, urinary SMCSO and several LC-MS features appeared as potentially promising biomarkers of broccoli consumption and demonstrated dose-response relationship. Future work should focus on validating these compounds as food intake biomarkers.PMID:37665045 | DOI:10.1039/d2fo03988e

Food Funct. 2023 Sep 4. doi: 10.1039/d3fo00406f. Online ahead of print.ABSTRACTWater pollution causes the propagation of pathogenic microorganisms, which poses a serious threat to human life. Escherichia coli O157:H7, as a representative organism that can directly exhibit molecular response to stress, was selected as the indicator bacteria for the study. Tandem mass tag (TMT) quantitative proteomics and non-targeted metabolomics were used to study the response of Escherichia coli O157:H7 to Aronia melanocarpa anthocyanin (AMA) treatment. The results showed that 628 proteins and 1338 metabolites changed significantly after treatment with AMAs. According to bioinformatics analysis, integrated proteomics and metabolomics analysis differentially expressed proteins (DEPs) and metabolites participate in pyruvate metabolism, glycolysis/gluconeogenesis, alanine, aspartate and glutamate metabolism and the pentose phosphate pathway. This study preliminarily proposed the inhibition mechanism of AMAs on Escherichia coli O157:H7 from the perspective of multi-omics, providing a theoretical basis for the application of natural preservatives in fresh cut vegetables.PMID:37664957 | DOI:10.1039/d3fo00406f

Anal Chem. 2023 Sep 4. doi: 10.1021/acs.analchem.3c02267. Online ahead of print.ABSTRACTThe development of ion mobility-mass spectrometry (IM-MS) has revolutionized the analysis of small molecules, such as metabolomics, lipidomics, and exposome studies. The curation of comprehensive reference collision cross-section (CCS) databases plays a pivotal role in the successful application of IM-MS for small-molecule analysis. In this study, we presented AllCCS2, an enhanced version of AllCCS, designed for the universal prediction of the ion mobility CCS values of small molecules. AllCCS2 incorporated newly available experimental CCS data, including 10,384 records and 7713 unified values, as training data. By leveraging a neural network trained on diverse molecular representations encompassing mass spectrometry features, molecular descriptors, and graph features extracted using a graph convolutional network, AllCCS2 achieved exceptional prediction accuracy. AllCCS2 achieved median relative error (MedRE) values of 0.31, 0.72, and 1.64% in the training, validation, and testing sets, respectively, surpassing existing CCS prediction tools in terms of accuracy and coverage. Furthermore, AllCCS2 exhibited excellent compatibility with different instrument platforms (DTIMS, TWIMS, and TIMS). The prediction uncertainties in AllCCS2 from the training data and the prediction model were comprehensively investigated by using representative structure similarity and model prediction variation. Notably, small molecules with high structural similarities to the training set and lower model prediction variation exhibited improved accuracy and lower relative errors. In summary, AllCCS2 serves as a valuable resource to support applications of IM-MS technologies. The AllCCS2 database and tools are freely accessible at http://allccs.zhulab.cn/.PMID:37664900 | DOI:10.1021/acs.analchem.3c02267

Front Endocrinol (Lausanne). 2023 Aug 17;14:1233613. doi: 10.3389/fendo.2023.1233613. eCollection 2023.ABSTRACTINTRODUCTION: We investigated the effects of hormonal and non-hormonal oral contraceptives (OCs) on bone mass, mineralization, composition, mechanical properties, and metabolites in pubertal female SD rats.METHODS: OCs were given for 3-, and 7 months at human equivalent doses. The combined hormonal contraceptive (CHC) was ethinyl estradiol and progestin, whereas the non-hormonal contraceptive (NHC) was ormeloxifene. MicroCT was used to assess bone microarchitecture and BMD. Bone formation and mineralization were assessed by static and dynamic histomorphometry. The 3-point bending test, nanoindentation, FTIR, and cyclic reference point indentation (cRPI) measured the changes in bone strength and material composition. Bone and serum metabolomes were studied to identify potential biomarkers of drug efficacy and safety and gain insight into the underlying mechanisms of action of the OCs.RESULTS: NHC increased bone mass in the femur metaphysis after 3 months, but the gain was lost after 7 months. After 7 months, both OCs decreased bone mass and deteriorated trabecular microarchitecture in the femur metaphysis and lumbar spine. Also, both OCs decreased the mineral: matrix ratio and increased the unmineralized matrix after 7 months. After 3 months, the OCs increased carbonate: phosphate and carbonate: amide I ratios, indicating a disordered hydroxyapatite crystal structure susceptible to resorption, but these changes mostly reversed after 7 months, indicating that the early changes contributed to demineralization at the later time. In the femur 3-point bending test, CHC reduced energy storage, resilience, and ultimate stress, indicating increased susceptibility to micro-damage and fracture, while NHC only decreased energy storage. In the cyclic loading test, both OCs decreased creep indentation distance, but CHC increased the average unloading slope, implying decreased microdamage risk and improved deformation resistance by the OCs. Thus, reduced bone mineralization by the OCs appears to affect bone mechanical properties under static loading, but not its cyclic loading ability. When compared to an age-matched control, after 7 months, CHC affected 24 metabolic pathways in bone and 9 in serum, whereas NHC altered 17 in bone and none in serum. 6 metabolites were common between the serum and bone of CHC rats, suggesting their potential as biomarkers of bone health in women taking CHC.CONCLUSION: Both OCs have adverse effects on various skeletal parameters, with CHC having a greater negative impact on bone strength.PMID:37664835 | PMC:PMC10470083 | DOI:10.3389/fendo.2023.1233613

Heliyon. 2023 Aug 9;9(8):e18909. doi: 10.1016/j.heliyon.2023.e18909. eCollection 2023 Aug.ABSTRACTAs major depressive disorder (MDD) is such a diverse condition, there are currently no clear ways for determining its severity, endophenotype, or therapy response. The distinctive nature of depression, the variability of analysis in literature and the large number of conceptually complicated biomarkers are some of the many reasons for the lack of progress. Markers are involved in the process of neurotrophic, metabolic, and inflammation as well as neuroendocrine and neurotransmitter systems' components. Some clinical indicators are strong enough so that can be measured using assessments of proteomic, genetic, metabolomics, neuroimaging, epigenetic and transcriptomic. Markers of oxidative stress, endocrine, inflammatory, proteomic, and growth indicators are currently among the promising biologic systems/markers identified in this analysis. This narrative review examines succinct studies which investigated cytokines of inflammatory factors, peripheral factors of development, metabolic and endocrine markers as pathophysiological biomarkers of MDD, and treatment responses. Endocrine and metabolic alterations have also been linked to MDD in various studies. So, this study summarizes all of the numerous biomarkers that are significant in the detection or treatment of MDD patients. The paper also provides an overview of various biomarkers which are important for the regulation and its effects on MDD.PMID:37664743 | PMC:PMC10469054 | DOI:10.1016/j.heliyon.2023.e18909

Heliyon. 2023 Aug 11;9(8):e19108. doi: 10.1016/j.heliyon.2023.e19108. eCollection 2023 Aug.ABSTRACTGrain-sized moxibustion (GS-Moxi) and suspended moxibustion (S-Moxi) represent the two typical local heat therapies in Traditional Chinese Medicine (TCM) and have been extensively used in treating gastric ulcers (GU) in China. However, the difference in biological response between the two moxibustion therapies in treating GU remains unclear. Here we investigated the therapeutic effect and potential mechanistic difference underlying the two moxibustion methods. Ethanol-induced GU model was established and was treated with GS-Moxi or S-Moxi at ST36 and ST21 for 5 days separately. And then, gastric histopathological examination, immunohistochemical staining for repair factors (EGFR, VEGF, Ki67), and 1H NMR-based metabolomics analysis of plasma and stomach of rats were conducted. We found GS-Moxi and S-Moxi effectively alleviated gastric damage and significantly increased the expression of related repair factors. However, S-Moxi corrected aberrant energy metabolism and lipids metabolism in GU rats but had little effect on neurotransmitter-related metabolism, while GS-Moxi regulated energy metabolism and neurotransmitter-related metabolism in GU rats but had no effect on lipids metabolism. We further proposed that the main target of S-Moxi may be liver and vasculature, whereas GS-Moxi specially targeted the stomach via regulating nervous system. This study strongly verified the outstanding gastroprotective effects of moxibustion and enriched our understanding of the varied biological responses triggered by different moxibustion methods.PMID:37664739 | PMC:PMC10469062 | DOI:10.1016/j.heliyon.2023.e19108