PubMed

J Anim Physiol Anim Nutr (Berl). 2022 Nov 16. doi: 10.1111/jpn.13789. Online ahead of print.ABSTRACTThe purpose of this study is to explore the potential plasma metabolism biomarkers reflecting the maintenance status of growing pigs. The repeated measurement design was used in this experiment, and six barrows (28.6 ± 0.5 kg BW) were selected and kept in metabolism crates. The feeding level in growing pigs close to ad libitum was 2400 kJ ME/kg BW0.6 ·day-1 during Day 1 to Day 7, while a feeding level of 782 kJ ME/kg BW0.6 ·day-1 was provided as energy requirement for maintenance during Day 8 to Day 14. Plasma samples of each pig were collected from the anterior vena cava on the morning of Day 8 and Day 15. The metabolites of plasma were determined by high-resolution mass spectrometry using a metabolomics approach. Results showed that metabolomics analysis between ad libitum-fed state and maintained status revealed differences in 16 compounds. Identified compounds were enriched in metabolic pathways related to linoleic acid metabolism, tryptophan metabolism, and alanine, aspartate and glutamate metabolism. In conclusion, linoleic acid metabolism, tryptophan metabolism, alanine, aspartate and glutamic acid metabolism pathways played a major regulatory role in the maintenance status of growing pigs. The potential metabolism biomarkers of maintenance in growing pigs were linoleic acid, glutamine and tyrosine.PMID:36382682 | DOI:10.1111/jpn.13789

Mol Omics. 2022 Nov 16. doi: 10.1039/d2mo00251e. Online ahead of print.ABSTRACTClubroot, a devastating soil-borne root disease, in Brassicaceae is caused by Plasmodiophora brassicae Woronin (P. brassicae W.), an obligate biotrophic protist. Plant growth and development, as well as seed yield of Brassica crops, are severely affected due to this disease. Several reports described the molecular responses of B. napus to P. brassicae; however, information on the early stages of pathogenesis is limited. In this study, we have used transcriptomics and metabolomics to characterize P. brassicae pathogenesis at 1-, 4-, and 7-days post-inoculation (DPI) in clubroot resistant (CR) and susceptible (CS) doubled-haploid (DH) canola lines. When we compared between inoculated and uninoculated groups, a total of 214 and 324 putative genes exhibited differential expression (q-value < 0.05) at one or more time-points in the CR and CS genotypes, respectively. When the inoculated CR and inoculated CS genotypes were compared, 4765 DEGs were differentially expressed (q-value < 0.05) at one or more time-points. Several metabolites related to organic acids (e.g., citrate, pyruvate), amino acids (e.g., proline, aspartate), sugars, and mannitol, were differentially accumulated in roots in response to pathogen infection when the CR and CS genotypes were compared. Several DEGs also corresponded to differentially accumulated metabolites, including pyrroline-5-carboxylate reductase (BnaC04g11450D), citrate synthase (BnaC02g39080D), and pyruvate kinase (BnaC04g23180D) as detected by transcriptome analysis. Our results suggest important roles for these genes in mediating resistance to clubroot disease. To our knowledge, this is the first report of an integrated transcriptome and metabolome analysis aimed at characterizing the molecular basis of resistance to clubroot in canola.PMID:36382681 | DOI:10.1039/d2mo00251e

AIDS. 2022 Dec 1;36(15):2089-2099. doi: 10.1097/QAD.0000000000003363. Epub 2022 Aug 18.ABSTRACTOBJECTIVE: Over 19 million individuals globally have a cocaine use disorder, a significant public health crisis. Cocaine has also been associated with a pro-inflammatory state and recently with imbalances in the intestinal microbiota as compared to nonuse. The objective of this pilot study was to characterize the gut microbiota and plasma metabolites in people with HIV (PWH) who use cocaine compared with those who do not.DESIGN: Cross-sectional study.METHODS: A pilot study in PWH was conducted on 25 cocaine users and 25 cocaine nonusers from the Miami Adult Studies on HIV cohort. Stool samples and blood plasma were collected. Bacterial composition was characterized using 16S rRNA sequencing. Metabolomics in plasma were determined using gas and liquid chromatography/mass spectrometry.RESULTS: The relative abundances of the Lachnopspira genus, Oscillospira genus, Bifidobacterium adolescentis species, and Euryarchaeota phylum were significantly higher in the cocaine- using PWH compared to cocaine-nonusing PWH. Cocaine-use was associated with higher levels of several metabolites: products of dopamine catabolism (3-methoxytyrosine and 3-methoxytyramine sulfate), phenylacetate, benzoate, butyrate, and butyrylglycine.CONCLUSIONS: Cocaine use was associated with higher abundances of taxa and metabolites known to be associated with pathogenic states that include gastrointestinal conditions. Understanding key intestinal bacterial functional pathways that are altered due to cocaine use in PWH will provide a better understanding of the relationships between the host intestinal microbiome and potentially provide novel treatments to improve health.PMID:36382433 | DOI:10.1097/QAD.0000000000003363

Mol Nutr Food Res. 2022 Nov 16:e2200508. doi: 10.1002/mnfr.202200508. Online ahead of print.ABSTRACTSCOPE: Molecular networking (MN) analysis intends to provide chemical insight of untargeted mass spectrometry (MS) data to the user's underlying biological questions. Foodomics is the study of chemical compounds in food using advanced omics methods. In this study, we developed an MS-MN-based foodomics approach to investigate the composition and anti-obesity activity of cannabinoids in hemp oil.METHODS AND RESULTS: A total of 16 cannabinoids were determined in optimized microwave pretreatment of hemp oil using the developed approach. Untargeted metabolomics analysis revealed that cannabinoid extract (CE) and its major constituent (cannabidiol, CBD), could alleviate high glucose-induced increases in lipids and carbohydrates, and decreases in amino acid and nucleic acid. Moreover, CE and CBD were also found to suppress the expression levels of mdt-15, sbp-1, fat-5, fat-6, fat-7, daf-2, and elevate the expression level of daf-1,daf-7, daf-16, sod-3, gst-4, lipl-4, resulting in the decrease of lipid synthesis and the enhance of kinetism. Canonical correspondence analysis (CCA) uncovered strong associations between specific metabolic alterations and gene expression levels.CONCLUSION: These findings from this exploratory study offered a new insight into the roles of cannabinoids in the treatment of obesity and related complications. This article is protected by copyright. All rights reserved.PMID:36382382 | DOI:10.1002/mnfr.202200508

Hepatol Commun. 2022 Nov 15. doi: 10.1002/hep4.2052. Online ahead of print.ABSTRACTA growing body of evidence has indicated an expanding functional network of B-cell lymphoma 2 (BCL-2) family proteins beyond regulation of cell death and survival. Here, we examined the role and mechanisms of BH3 interacting-domain death agonist (BID), a pro-death BCL-2 family member, in the development of diet-induced metabolic dysfunction. Mice deficient in bid (bid-/- ) were resistant to high-fat diet (HFD)-induced obesity, hepatic steatosis, and dyslipidemia with an increased insulin sensitivity. Indirect calorimetry analysis indicated that bid deficiency increased metabolic rate and decreased respiratory exchange ratio, suggesting a larger contribution of lipids to overall energy expenditure. While expression of several genes related to lipid accumulation was only increased in wild-type livers, metabolomics analysis revealed a consistent reduction in fatty acids but an increase in certain sugars and Krebs cycle intermediates in bid-/- livers. Gut microbiota (GM) analysis indicated that HFD induced gut dysbiosis with differential patterns in wild-type and in bid-/- mice. Notably, abrogation of GM by antibiotics during HFD feeding eliminated the beneficial effects against obesity and hepatic steatosis conferred by the bid deficiency. Conclusion: These results indicate that the protective role of bid-deficiency against diet-induced metabolic dysfunction interacts with the function of GM.PMID:36382356 | DOI:10.1002/hep4.2052

Biomed Rep. 2022 Oct 14;17(6):95. doi: 10.3892/br.2022.1578. eCollection 2022 Dec.ABSTRACTTargeted therapies are becoming more common and genetic tumor profiling is becoming more precise and affordable. The aim of the present review was to demonstrate the importance of molecular analyses in tumors, summarize the current situation, provide an outlook on how to improve diagnosis to facilitate individualized therapy, including the use of specific methodologies for tumor marker analysis to improve patient treatment. Most predicted metabolomic and proteomic biomarkers have not progressed from the laboratory to clinical trials, as most of the trials were stopped at the initial stage of biomarker identification. The use of liquid biopsies as a clinical tool improves cancer screening, diagnosis and prognosis; furthermore, is able to improve the classification of more diverse disease entities, assess therapy response and identify treatment-resistant clones, allowing for more stringent patient monitoring. Based on specific clinical populations and the unique molecular features of a cancer, the identification of a suitable targeted therapy may be accomplished. The present review provides insight into cancer genomic testing in the clinical setting and the available methods, supporting the prioritization of molecular therapeutic tumor targeting.PMID:36382257 | PMC:PMC9634049 | DOI:10.3892/br.2022.1578

Comput Struct Biotechnol J. 2022 Oct 25;20:5935-5951. doi: 10.1016/j.csbj.2022.10.030. eCollection 2022.ABSTRACTGlycolipid metabolism disorder are major threats to human health and life. Genetic, environmental, psychological, cellular, and molecular factors contribute to their pathogenesis. Several studies demonstrated that neuroendocrine axis dysfunction, insulin resistance, oxidative stress, chronic inflammatory response, and gut microbiota dysbiosis are core pathological links associated with it. However, the underlying molecular mechanisms and therapeutic targets of glycolipid metabolism disorder remain to be elucidated. Progress in high-throughput technologies has helped clarify the pathophysiology of glycolipid metabolism disorder. In the present review, we explored the ways and means by which genomics, transcriptomics, proteomics, metabolomics, and gut microbiomics could help identify novel candidate biomarkers for the clinical management of glycolipid metabolism disorder. We also discuss the limitations and recommended future research directions of multi-omics studies on these diseases.PMID:36382190 | PMC:PMC9646750 | DOI:10.1016/j.csbj.2022.10.030

Comput Struct Biotechnol J. 2022 Oct 25;20:5847-5858. doi: 10.1016/j.csbj.2022.10.026. eCollection 2022.ABSTRACTBACKGROUND: Bifidobacterium longum BB536 supplementation can be used to regulate bowel movements in various people, including healthy subjects and patients with irritable bowel syndrome (IBS); however, individuals vary in their responses to B. longum BB536 treatment. One putative factor is the gut microbiota; recent studies have reported that the gut microbiota mediates the effects of diet or drugs on the host. Here, we investigated intestinal features, such as the microbiome and metabolome, related to B. longum BB536 effectiveness in increasing bowel movement frequency.RESULTS: A randomized, double-blind controlled crossover trial was conducted with 24 adults who mainly tended to be constipated. The subjects received a two-week dietary intervention consisting of B. longum BB536 in acid-resistant seamless capsules or similarly encapsulated starch powder as the placebo control. Bowel movement frequency was recorded daily, and fecal samples were collected at several time points, and analyzed by metabologenomic approach that consists of an integrated analysis of metabolome data obtained using mass spectrometry and microbiome data obtained using high-throughput sequencing. There were differences among subjects in B. longum intake-induced bowel movement frequency. The responders were predicted by machine learning based on the microbiome and metabolome features of the fecal samples collected before B. longum intake. The abundances of eight bacterial genera were significantly different between responders and nonresponders.CONCLUSIONS: Intestinal microbiome and metabolome profiles might be utilized as potential markers of improved bowel movement after B. longum BB536 supplementation. These findings have implications for the development of personalized probiotic treatments.PMID:36382178 | PMC:PMC9636538 | DOI:10.1016/j.csbj.2022.10.026

Neurooncol Adv. 2022 Oct 11;4(1):vdac163. doi: 10.1093/noajnl/vdac163. eCollection 2022 Jan-Dec.ABSTRACTBACKGROUND: Hyperglycemia has been associated with worse survival in glioblastoma. Attempts to lower glucose yielded mixed responses which could be due to molecularly distinct GBM subclasses.METHODS: Clinical, laboratory, and molecular data on 89 IDH-wt GBMs profiled by clinical next-generation sequencing and treated with Stupp protocol were reviewed. IDH-wt GBMs were sub-classified into RTK I (Proneural), RTK II (Classical) and Mesenchymal subtypes using whole-genome DNA methylation. Average glucose was calculated by time-weighting glucose measurements between diagnosis and last follow-up.RESULTS: Patients were stratified into three groups using average glucose: tertile one (<100 mg/dL), tertile two (100-115 mg/dL), and tertile three (>115 mg/dL). Comparison across glucose tertiles revealed no differences in performance status (KPS), dexamethasone dose, MGMT methylation, or methylation subclass. Overall survival (OS) was not affected by methylation subclass (P = .9) but decreased with higher glucose (P = .015). Higher glucose tertiles were associated with poorer OS among RTK I (P = .08) and mesenchymal tumors (P = .05), but not RTK II (P = .99). After controlling for age, KPS, dexamethasone, and MGMT status, glucose remained significantly associated with OS (aHR = 5.2, P = .02). Methylation clustering did not identify unique signatures associated with high or low glucose levels. Metabolomic analysis of 23 tumors showed minimal variation across metabolites without differences between molecular subclasses.CONCLUSION: Higher average glucose values were associated with poorer OS in RTKI and Mesenchymal IDH-wt GBM, but not RTKII. There were no discernible epigenetic or metabolomic differences between tumors in different glucose environments, suggesting a potential survival benefit to lowering systemic glucose in selected molecular subtypes.PMID:36382106 | PMC:PMC9653172 | DOI:10.1093/noajnl/vdac163

Cureus. 2022 Oct 4;14(10):e29927. doi: 10.7759/cureus.29927. eCollection 2022 Oct.ABSTRACTHypertension (HTN) is one of the most prevalent and dangerous cardiovascular diseases worldwide. Recently, its direct or indirect association with gut dysbiosis has been an interest of study for many. It also includes the metabolomic and functional gene changes in hypertensives compared with healthy individuals. This systematic review aims to study quantitative and qualitative interactions between the two and re-defining the heart-gut axis. We have strictly followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), 2020, guidelines. We conducted an in-depth search of databases such as PubMed, PubMed Central (PMC), Medline, and ScienceDirect to find relevant studies for our topic of interest. After the final quality check, we included eight articles in the systematic review. A significant difference in richness and diversity in gut microbiota was observed in hypertensive patients compared with healthy controls. There was an increased abundance of many bacteria such as Catabacter, Robinsoleilla, Serratia, Enterobacteriaceae, Ruminococcus torques, Parasutterella, Escherichia, Shigella, and Klebsiella, while a decreased abundance of Sporobacter, Roseburia hominis, Romboutsia spp., and Roseburia. Alteration of the composition also varied based on diet, age, ethnicity, and severity of HTN. Short-chain fatty acids (SCFAs)-producing bacteria are found to be on the lower side in hypertensives owing to the protective property of SCFAs against inflammation, especially butyric acid. From the perspective of metabolomic changes, harmful metabolites for cardiovascular health such as intestinal fatty acid binding protein (I-FABP), lipopolysaccharides (LPSs), zonulin, sphingomyelins, acylcarnitines, and trimethylamine N-oxide (TMAO) were found to be increased in hypertensives. Changes in these biomarkers further establish the relation between gut epithelial health and high blood pressure (BP). Participants affected by diseases have an overall lower rate of acquiring new genes, which results in a low richness of genes in them compared with healthy individuals. There is increased expression of the choline utilization (cutC) gene and reduced expression of genes associated with biosynthesis and transport of amino acids in high-BP participants. The unique changes in the composition of the microbiota, functional changes in genes, and metabolome collectively help for a better understanding of the pathogenesis of HTN and also suggest the gut as a promising new therapeutic target for HTN. To establish a further causal relationship between the two, more research is required.PMID:36381851 | PMC:PMC9642844 | DOI:10.7759/cureus.29927

Ecol Evol. 2022 Nov 8;12(11):e9475. doi: 10.1002/ece3.9475. eCollection 2022 Nov.ABSTRACTTrees and shrubs in suburban forests can be subject to chronic herbivory from abundant white-tailed deer, influencing survival, growth, secondary metabolites, and ecological success in the community. We investigated how deer affect the size, cover, and metabolomes of four species in the understory of a suburban forest in central New Jersey, USA: the woody shrubs Euonymus alatus and Lindera benzoin, the tree Nyssa sylvatica, and the semi-woody shrub Rosa multiflora. For each species, we compared plants in 38 16 m2 plots with or without deer exclosure, measuring proportion cover and mean height after 6.5 years of fencing. We scored each species in all plots for deer browsing over 8 years and assessed selection by deer among the species. We did untargeted metabolomics by sampling leaves from three plants of each species in an equal number of fenced and unfenced plots, conducting chloroform-methanol extractions followed by LC-MS/MS, and conducting statistical analysis on MetaboAnalyst. The proportion of a species browsed ranged from 0.24 to 0.35. Nyssa sylvatica appeared most selected by and susceptible to deer; in unfenced plots, both its cover and mean height were significantly lower. Only cover or height was lower for E. alatus and L. benzoin in unfenced plots, while R. multiflora height was greater. The metabolomic analysis identified 2333 metabolites, which clustered by species but not fencing treatment. However, targeted analysis of the top metabolites grouped by fencing for all samples and for each species alone and was especially clear in N. sylvatica, which also grouped by fencing using all metabolites. The most significant metabolites that were upregulated in fenced plants include some involved in defense-related metabolic pathways, e.g., monoterpenoid biosynthesis. In overbrowsed suburban forests, variation of deer impact on species' ecological success, potentially mediated by metabolome-wide chemical responses to deer, may contribute to changes in community structure.PMID:36381402 | PMC:PMC9643135 | DOI:10.1002/ece3.9475

Neurooncol Adv. 2022 Nov 11;4(Suppl 2):ii73-ii80. doi: 10.1093/noajnl/vdac036. eCollection 2022 Nov.ABSTRACTBACKGROUND: Understanding the trajectory and development of disease is important and the knowledge can be used to find novel targets for therapy and new diagnostic tools for early diagnosis.METHODS: Large cohorts from different parts of the world are unique assets for research as they have systematically collected plasma and DNA over long-time periods in healthy individuals, sometimes even with repeated samples. Over time, the population in the cohort are diagnosed with many different diseases, including brain tumors.RESULTS: Recent studies have detected genetic variants that are associated with increased risk of glioblastoma and lower grade gliomas specifically. The impact for genetic markers to predict disease in a healthy population has been deemed low, and a relevant question is if the genetic variants for glioma are associated with risk of disease or partly consist of genes associated to survival. Both metabolite and protein spectra are currently being explored for early detection of cancer.CONCLUSIONS: We here present a focused review of studies of genetic variants, metabolomics, and proteomics studied in prediagnostic glioma samples and discuss their potential in early diagnostics.PMID:36380862 | PMC:PMC9650466 | DOI:10.1093/noajnl/vdac036

BMC Microbiol. 2022 Nov 15;22(1):275. doi: 10.1186/s12866-022-02691-y.ABSTRACTBACKGROUND: Wickerhamomyces anomalus (W. anomalus) is a kind of non-Saccharomyces yeast that has a variety of unique physiological characteristics and metabolic features and is widely used in many fields, such as food preservation, biomass energy, and aquaculture feed protein production. However, the mechanism of W. anomalus response to ethanol stress is still unclear, which greatly limits its application in the production of ethanol beverages and ethanol fuels. Therefore, we checked the effects of ethanol stress on the morphology, the growth, and differentially expressed genes (DEGs) and metabolites (DEMs) of W. anomalus.RESULTS: High concentrations of ethanol (9% ethanol and 12% ethanol) remarkably inhibited the growth of W. anomalus. Energy metabolism, amino acid metabolism, fatty acids metabolism, and nucleic acid metabolism were significantly influenced when exposing to 9% ethanol and 12% ethanolstress, which maybe universal for W. anomalus to response to different concentrations of ethanol stressl Furthermore, extracellular addition of aspartate, glutamate, and arginine significantly abated ethanol damage and improved the survival rate of W. anomalus.CONCLUSIONS: The results obtained in this study provide insights into the mechanisms involved in W. anomalus response to ethanol stress. Therefore, new strategies can be realized to improve the ethanol tolerance of W. anomalus through metabolic engineering.PMID:36380285 | DOI:10.1186/s12866-022-02691-y

BMC Plant Biol. 2022 Nov 15;22(1):530. doi: 10.1186/s12870-022-03909-x.ABSTRACTBACKGROUND: The rich yellow-orange to vividly deep red bark of willow (Salix spp.) branches have high ornamental and economic value. However, the mechanism underlying the regulation of willow branch color remains unknown. Therefore, we performed metabolomics and transcriptomics analyses of purple, green, and red willow barks to elucidating the mechanisms regulating color development.RESULTS: Seven anthocyanins were isolated; pelargonidin, petunidin 3-O-rutinoside, and cyanin chloride were the most abundant in red bark, whereas pelargonin chloride was most abundant in purple bark. The green bark contained the highest level of malvidin; however, the malvidin level was not significantly higher than in the red bark. The purple bark contained the largest amount of canthaxanthin, a carotenoid pigment. The integrated pathways of flavonoid biosynthesis, carotenoid biosynthesis, and porphyrin and chlorophyll metabolism were constructed for the willow barks. Among the three barks, the expression of the structural genes ANS, ANR, and BZ1, which are involved in anthocyanin synthesis, was the highest in red bark, likely causing anthocyanin accumulation. The expression of CrtZ, which participates in the carotenoid pathway, was the highest in purple bark, likely leading to canthaxanthin accumulation. The high expression of DVR, POR, and CRD1 may be associated with green pigment synthesis in the chlorophyll biosynthesis pathway.CONCLUSIONS: Purple bark color is co-regulated by anthocyanins and carotenoids, whereas red bark is characterized by anthocyanin accumulation and chlorophyll degradation. The green pigment is regulated by maintaining chlorophyll synthesis. BZ1 and CrtZ are candidate genes regulating anthocyanin and canthaxanthin accumulation in red and purple barks respectively. Collectively, our results may facilitate the genetic breeding and cultivation of colorful willows with improved color and luster.PMID:36380271 | DOI:10.1186/s12870-022-03909-x

Commun Biol. 2022 Nov 15;5(1):1250. doi: 10.1038/s42003-022-04179-x.ABSTRACTT-cell-driven immune responses are responsible for several autoimmune disorders, such as psoriasis vulgaris and rheumatoid arthritis. Identification of metabolic signatures in inflamed tissues is needed to facilitate novel and individualised therapeutic developments. Here we show the temporal metabolic dynamics of T-cell-driven inflammation characterised by nuclear magnetic resonance spectroscopy-based metabolomics, histopathology and immunohistochemistry in acute and chronic cutaneous delayed-type hypersensitivity reaction (DTHR). During acute DTHR, an increase in glutathione and glutathione disulfide is consistent with the ear swelling response and degree of neutrophilic infiltration, while taurine and ascorbate dominate the chronic phase, suggesting a switch in redox metabolism. Lowered amino acids, an increase in cell membrane repair-related metabolites and infiltration of T cells and macrophages further characterise chronic DTHR. Acute and chronic cutaneous DTHR can be distinguished by characteristic metabolic patterns associated with individual inflammatory pathways providing knowledge that will aid target discovery of specialised therapeutics.PMID:36380134 | DOI:10.1038/s42003-022-04179-x

Eye (Lond). 2022 Nov 15. doi: 10.1038/s41433-022-02307-9. Online ahead of print.ABSTRACTCorneal and ocular surface diseases (OSDs) carry significant psychosocial and economic burden worldwide. We set out to review the literature on the application of artificial intelligence (AI) and bioinformatics for analysis of biofluid biomarkers in corneal and OSDs and evaluate their utility in clinical decision making. MEDLINE, EMBASE, Cochrane and Web of Science were systematically queried for articles using AI or bioinformatics methodology in corneal and OSDs and examining biofluids from inception to August 2021. In total, 10,264 articles were screened, and 23 articles consisting of 1058 individuals were included. Using various AI/bioinformatics tools, changes in certain tear film cytokines that are proinflammatory such as increased expression of apolipoprotein, haptoglobin, annexin 1, S100A8, S100A9, Glutathione S-transferase, and decreased expression of supportive tear film components such as lipocalin-1, prolactin inducible protein, lysozyme C, lactotransferrin, cystatin S, and mammaglobin-b, proline rich protein, were found to be correlated with pathogenesis and/or treatment outcomes of dry eye, keratoconus, meibomian gland dysfunction, and Sjögren's. Overall, most AI/bioinformatics tools were used to classify biofluids into diseases subgroups, distinguish between OSD, identify risk factors, or make predictions about treatment response, and/or prognosis. To conclude, AI models such as artificial neural networks, hierarchical clustering, random forest, etc., in conjunction with proteomic or metabolomic profiling using bioinformatics tools such as Gene Ontology or Kyoto Encylopedia of Genes and Genomes pathway analysis, were found to inform biomarker discovery, distinguish between OSDs, help define subgroups with OSDs and make predictions about treatment response in a clinical setting.PMID:36380089 | DOI:10.1038/s41433-022-02307-9

Pharmacol Res. 2022 Nov 12:106554. doi: 10.1016/j.phrs.2022.106554. Online ahead of print.ABSTRACTPancreatic cancer (PC) is one of the most malignant cancers, owing to extremely high aggressiveness and mortality. Yet, this condition currently incurs widely drug resistance and therapeutic deficiency. In this study, we proposed a novel functional metabolomics strategy as Spatial Temporal Operative Real Metabolomics (STORM) to identify the determinant functional metabolites in a dynamic and visualized pattern whose level changes are mechanistically associated with therapeutic efficiency of gemcitabine against PC. Integrating quantitative analysis and spatial-visualization characterization of functional metabolites in vivo, we identified that the AMP-cAMP axis was a novel therapeutic target of PC to intermediate therapeutic efficiency of gemcitabine. Gemcitabine could induce the dual accumulation of cyclic AMP (cAMP) and AMP in tumor tissues. Quantitative analysis of associated biosynthetic enzymes and genes revealed that two independent intracellular ATP derived biosynthetic pathways to promote the dual activation of AMP-cAMP axis in a lower-level energetic environment. Then, gemcitabine induced the dual accumulation of AMP and cAMP can separately activate signaling pathways of AMPK and PKA, leading to the inhibition of tumor growth by the upregulation of the downstream tumor suppressor GADD45A. Collectively, our new STORM strategy was the first time to identify novel target of PC from a metabolic perspective as the dual activation of AMP-cAMP axis induced by gemcitabine can efficiently suppress PC tumor growth. In addition, such discovery has the capability to lower drug resistance of gemcitabine by specifically interacting with novel target, contributing to the improvement of therapeutic efficiency.PMID:36379357 | DOI:10.1016/j.phrs.2022.106554

Sci Total Environ. 2022 Nov 12:160090. doi: 10.1016/j.scitotenv.2022.160090. Online ahead of print.ABSTRACTOcean acidification has become a major ecological and environmental problem in the world, whereas the impact mechanism of ocean acidification in marine bivalves is not fully understood. Cellular energy allocation (CEA) approach and high-coverage metabolomic techniques were used to investigate the acidification effects on the energy metabolism of mussels. The thick shell mussels Mytilus coruscus were exposed to seawater pH 8.1 (control) and pH 7.7 (acidification) for 14 days and allowed to recover at pH 8.1 for 7 days. The levels of carbohydrates, lipids and proteins significantly decreased in the digestive glands of the mussels exposed to acidification. The 14-day acidification exposure increased the energy demands of mussels, resulting in increased electron transport system (ETS) activity and decreased cellular energy allocation (CEA). Significant carry-over effects were observed on all cellular energy parameters except the concentration of carbohydrates and cellular energy demand (Ec) after 7 days of recovery. Metabolomic analysis showed that acidification affected the phenylalanine, tyrosine and tryptophan biosynthesis, taurine and hypotaurine metabolism, and glycine, serine and threonine metabolism. Correlation analysis showed that mussel cell energy parameters (carbohydrates, lipids, proteins, CEA) were negatively/positively correlated with certain differentially abundant metabolites. Overall, the integrated biochemical and metabolomics analyses demonstrated the negative effects of acidification on energy metabolism at the cellular level and implicated the alteration of biosynthesis and metabolism of amino acids as a mechanism of metabolic perturbation caused by acidification in mussels.PMID:36379341 | DOI:10.1016/j.scitotenv.2022.160090

Phytochemistry. 2022 Nov 12:113500. doi: 10.1016/j.phytochem.2022.113500. Online ahead of print.ABSTRACTHypericum species (Hypericaceae) are a group of important plants with medicinal, edible, and ornamental values. A phytochemical study on the whole plants of H. hengshanense W. T. Wang, a species endemic to China, led to the isolation and elucidation of 25 monoterpenoid acylphloroglucinols (MAPs). Among them, 10 are undescribed compounds, namely hyphengshanols A-D, (+)-empetrilatinol A, (-)-empetrilatinol B, (-)-hyperjovinol A, (9S,2'S)-dauphinol F, and (8R,2'S)-empetrikathiforin. In addition, the absolute configurations of other six compounds were firstly determined in the current study. The structures were established by ultraviolet (UV), high resolution electrospray ionization mass spectrum (HR-ESI-MS), and nuclear magnetic resonance spectroscopy (NMR) data. The absolute configurations were determined by experimental and calculated electronic circular dichroism (ECD) data analyses. Cytotoxicity assays on five human cell lines HL-60, A549, SMMC-7721, MDA-MB-231, and SW480 revealed that 16 compounds exhibited broad-spectrum antiproliferative activities with IC50 ranging from 7.54 to 45.70 μM.PMID:36379320 | DOI:10.1016/j.phytochem.2022.113500

Environ Pollut. 2022 Nov 12:120656. doi: 10.1016/j.envpol.2022.120656. Online ahead of print.ABSTRACTHeavy metals are widely distributed in soil ecosystems, posing a potential threat to soil biota. Micro- and nano-plastics (MNPs) can impact the accumulation of heavy metals in plants through changing soil microbial community and cause injury to plants. In this work, two concentrations (100 and 1000 mg/kg) polystyrene microplastics (PS-MPs) and nanoplastics (PS-NPs) were adopted to explore the effects and mechanisms of MNPs on the uptake of Cu, Zn, Pb and Cd in lettuce (Lactuca sativa L.). MPs increased the uptake of heavy metals in lettuce by increasing the relative abundance of the key metal-activation bacteria in rhizospheric soil. At the end of experiment, the contents of Cu, Zn, Pb and Cd in NP treatments were significantly (p < 0.05) higher than that of MPs, particularly in 1000 mg/kg of NPs, with concentrations of 52.6, 174, 10.3, and 33.2 mg/kg, respectively. Biomarkers and gene expression reveled that 1000 mg/kg of NPs caused more severe injuries to lettuce plant at the end. Moreover, metabolomic analysis demonstrated that NPs disturbed the metabolism of ATP-binding cassette transporter (ABC transporter) and plant hormone signal transduction of lettuce root, causing increased uptake of heavy metals by lettuce. This work reveals that MPs may increase accumulation of heavy metals by altering the rhizosphere microorganisms, whereas NPs increase accumulation of heavy metals by causing more severe injuries to lettuce plant.PMID:36379290 | DOI:10.1016/j.envpol.2022.120656