PubMed

Expert Rev Mol Diagn. 2023 Mar 24. doi: 10.1080/14737159.2023.2195553. Online ahead of print.ABSTRACTINTRODUCTION: Lipidomics focuses on the in-depth analysis of lipids, which are crucial macromolecules involved in a wide range of metabolic pathways. The increased intracellular accumulation of different classes of lipids in renal cell carcinoma (RCC) and prostate cancer (PCa) cells may be caused by elevated absorption or by increased de novo lipogenesis as a consequence of lipid metabolism reprogramming. The involvement of cholesterol metabolism in cancer's aberrant pathways has also been demonstrated.AREAS COVERED: This review provides an update on the most important lipidomics studies and applications in RCC and PCa, with a particular focus on how knowledge of aberrant lipid pathways may be used to identify biomarkers and novel therapeutic targets. In addition, the application of this methodologies have led to novel cancer subtypes identification and patient's risk stratification. Tracking tumor progression using specific biofluid metabolite profiles offers a huge translational opportunity for urological malignancies.EXPERT OPINION: Lipidomics is a promising branch of "omics" approach and should include in next decade new standardized analysis methods and randomized clinical trials in order to reach the aim to use this high-throughput technique in patient-tailored therapy perspective.PMID:36960789 | DOI:10.1080/14737159.2023.2195553

Plant Commun. 2023 Mar 23:100594. doi: 10.1016/j.xplc.2023.100594. Online ahead of print.ABSTRACTCrassulacean acid metabolism (CAM) has high water-use efficiency (WUE), which is widely recognized to have evolved from C3 photosynthesis. Different plant lineages have convergently evolved CAM, but the molecular mechanism underlying the C3-to-CAM evolution remains elusive. Platycerium bifurcatum (elkhorn fern) provides an opportunity to study molecular changes underlying the transition from C3 to CAM photosynthesis, because these two modes of photosynthesis occur in this species, with sporotrophophyll leaves (SLs) and cover leaves (CLs) performing C3 and weak CAM photosynthesis, respectively. Here, we report that the physiological and biochemical attributes of CAM in weak CAM-performing CLs were different from those in strong CAM species. We investigated the diel dynamics of the metabolome, proteome, and transcriptome in these dimorphic leaves within the same genetic background and under identical environmental conditions. We found that multi-omic diel dynamics in P. bifurcatum are subjected to both tissue and diel effects. Our analysis revealed temporal rewiring of biochemistry relevant to the energy-producing pathway (TCA cycle), CAM pathway, and stomatal movement in CLs in comparison with SLs. Also, we confirmed that PHOSPHOENOLPYRUVATE CARBOXYLASE KINASE (PPCK) exhibits convergence in gene expression among highly divergent CAM lineages. Our gene regulatory network analysis identified candidate transcription factors regulating the CAM pathway and stomatal movement. Taken together, our results provide new insights into weak CAM photosynthesis, and new avenues for CAM bioengineering.PMID:36960529 | DOI:10.1016/j.xplc.2023.100594

Front Nutr. 2023 Mar 7;10:1132527. doi: 10.3389/fnut.2023.1132527. eCollection 2023.ABSTRACTIn the production of soy sauce-aroma type baijiu (SSAB), the quality of base liquor significantly affects the finished liquor's quality. Moreover, low-quality liquor may cause health problems. The different quality grades of base liquor were analyzed to investigate the relationship between the quality and the key compounds in SSAB. In this study, samples were evaluated by the sensory and further analyzed by headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS) coupled with electronic nose (E-nose). First, by sensory evaluation, the sauce, floral and fruity, fermented aromas and taste indicators (softness, fullness, harmony, purity and persistence) were positively correlated with the quality grade of the base liquor. The E-nose could distinguish the different quality grades of base liquor well. Second, differential compounds were identified via untargeted metabolome based on the HS-SPME-GC-MS. 16 common differential compounds were shared in the base liquor from different fermentation rounds, including 11 esters, 1 alcohol, 2 aldehydes and 2 ketones. It was found that the higher the quality grade of the base liquor, the richer the content of aromatics, alcohols, aldehydes and ketones. The principal component analysis (PCA) biplots of the differential compounds in the different quality grades of base liquor indicated that the superior-grade base liquor has a strong fruity aroma. By correlation analysis of the differential compounds and sensors responses of E-nose, furfuryl ethyl ether, butanoic acid ethyl ester, isopentyl hexanoate, nonanoic acid ethyl ester and 3-methyl-1-butanol had a significant effect on the response intensity of E-nose sensors. In the present study, the key differential compounds between the different quality grades of base liquor were identified, and the sensory differences between the base liquor were digitized.PMID:36960200 | PMC:PMC10028209 | DOI:10.3389/fnut.2023.1132527

Front Mol Biosci. 2023 Mar 7;10:1130781. doi: 10.3389/fmolb.2023.1130781. eCollection 2023.ABSTRACTData-Dependent and Data-Independent Acquisition modes (DDA and DIA, respectively) are both widely used to acquire MS2 spectra in untargeted liquid chromatography tandem mass spectrometry (LC-MS/MS) metabolomics analyses. Despite their wide use, little work has been attempted to systematically compare their MS/MS spectral annotation performance in untargeted settings due to the lack of ground truth and the costs involved in running a large number of acquisitions. Here, we present a systematic in silico comparison of these two acquisition methods in untargeted metabolomics by extending our Virtual Metabolomics Mass Spectrometer (ViMMS) framework with a DIA module. Our results show that the performance of these methods varies with the average number of co-eluting ions as the most important factor. At low numbers, DIA outperforms DDA, but at higher numbers, DDA has an advantage as DIA can no longer deal with the large amount of overlapping ion chromatograms. Results from simulation were further validated on an actual mass spectrometer, demonstrating that using ViMMS we can draw conclusions from simulation that translate well into the real world. The versatility of the Virtual Metabolomics Mass Spectrometer (ViMMS) framework in simulating different parameters of both Data-Dependent and Data-Independent Acquisition (DDA and DIA) modes is a key advantage of this work. Researchers can easily explore and compare the performance of different acquisition methods within the ViMMS framework, without the need for expensive and time-consuming experiments with real experimental data. By identifying the strengths and limitations of each acquisition method, researchers can optimize their choice and obtain more accurate and robust results. Furthermore, the ability to simulate and validate results using the ViMMS framework can save significant time and resources, as it eliminates the need for numerous experiments. This work not only provides valuable insights into the performance of DDA and DIA, but it also opens the door for further advancements in LC-MS/MS data acquisition methods.PMID:36959982 | PMC:PMC10027714 | DOI:10.3389/fmolb.2023.1130781

Front Plant Sci. 2023 Mar 7;14:1120166. doi: 10.3389/fpls.2023.1120166. eCollection 2023.ABSTRACTKiwifruit is a climacteric fruit, in which the accumulation of flavor substances mainly occurs at the postharvest ripening stage. However, the dynamic changes in metabolite composition remain poorly understood. Here, targeted multi-platform metabolome analysis based on GC-MS and UPLC-MS/MS and enzyme activity analysis were performed at different postharvest ripening stages of kiwifruit. A total of 12 soluble sugars and 31 organic acids were identified. The main soluble sugars are sucrose, glucose and fructose, which exhibited similar variation tendencies along with the extension of ripening. The main organic acids are citric acid, quinic acid and malic acid, which showed different variation patterns. A total of 48 energy metabolites were identified, which were classified into two groups based on the content variation. The content of substances related to the respiratory metabolic pathway decreased gradually along with postharvest ripening, and there was obvious accumulation of downstream products such as amino acids at the late ripening stage. A total of 35 endogenous hormones were identified, among which seven cytokinins were highly accumulated at the later stage of softening. We further investigated the dynamic changes in the activities of 28 ripening-related enzymes. As a result, the activities of 13 enzymes were highly correlated with changes in starch, total pectin, and soluble sugars, and those of seven enzymes were closely associated with the change in firmness. In conclusion, this study comprehensively describes the dynamic changes in soluble sugars, organic acids, hormones, energy substances, and ripening-related enzyme activities during kiwifruit postharvest ripening, and provides a theoretical basis for the postharvest quality improvement of kiwifruit.PMID:36959943 | PMC:PMC10028114 | DOI:10.3389/fpls.2023.1120166

Front Plant Sci. 2023 Mar 7;14:1130924. doi: 10.3389/fpls.2023.1130924. eCollection 2023.ABSTRACTINTRODUCTION: Plants and arbuscular mycorrhizal fungi (AMF) mutualistic interactions are essential for sustainable agriculture production. Although it is shown that AMF inoculation improves cassava physiological performances and yield traits, the molecular mechanisms involved in AM symbiosis remain largely unknown. Herein, we integrated metabolomics and transcriptomics analyses of symbiotic (Ri) and asymbiotic (CK) cassava roots and explored AM-induced biochemical and transcriptional changes.RESULTS: Three weeks (3w) after AMF inoculations, proliferating fungal hyphae were observable, and plant height and root length were significantly increased. In total, we identified 1,016 metabolites, of which 25 were differentially accumulated (DAMs) at 3w. The most highly induced metabolites were 5-aminolevulinic acid, L-glutamic acid, and lysoPC 18:2. Transcriptome analysis identified 693 and 6,481 differentially expressed genes (DEGs) in the comparison between CK (3w) against Ri at 3w and 6w, respectively. Functional enrichment analyses of DAMs and DEGs unveiled transport, amino acids and sugar metabolisms, biosynthesis of secondary metabolites, plant hormone signal transduction, phenylpropanoid biosynthesis, and plant-pathogen interactions as the most differentially regulated pathways. Potential candidate genes, including nitrogen and phosphate transporters, transcription factors, phytohormone, sugar metabolism-related, and SYM (symbiosis) signaling pathway-related, were identified for future functional studies.DISCUSSION: Our results provide molecular insights into AM symbiosis and valuable resources for improving cassava production.PMID:36959933 | PMC:PMC10028151 | DOI:10.3389/fpls.2023.1130924

J Exp Bot. 2023 Mar 24:erad108. doi: 10.1093/jxb/erad108. Online ahead of print.ABSTRACTAnthracnose is a widespread plant disease caused by various species of the fungal pathogen Colletotrichum spp. In solanaceous plants such as tomato (Solanum lycopersicum), Colletotrichum infections exhibit a quiescent, asymptomatic state in developing fruit, followed by a transition to necrotrophic infections in ripe fruit. Through analysis of fruit tissue extracts of 95L368, a tomato breeding line that yields fruit with enhanced anthracnose resistance, we identified a role for steroidal glycoalkaloids (SGAs) in anthracnose resistance. The SGA α-tomatine and several of its derivatives accumulated at higher levels, in comparison to fruit of the susceptible tomato cultivar US28, 95L368 fruit extracts with fungistatic activity against Colletotrichum. Correspondingly, ripe and unripe 95L368 fruit displayed enhanced expression of glycoalkaloid metabolic enzyme (GAME) genes, which encode key enzymes in SGA biosynthesis. Metabolomics analysis incorporating recombinant inbred lines (RILs) generated from 95L368 and US28 yielded strong positive correlations between anthracnose resistance and accumulation of α-tomatine and several derivatives. Lastly, transient silencing of expression of the GAME genes GAME31 and GAME5 in anthracnose-susceptible tomato fruit yielded enhancements to anthracnose resistance. Together, our data support a role for SGAs in anthracnose defense in tomato, with a distinct SGA metabolomic profile conferring resistance to virulent Colletotrichum infections in ripe fruit.PMID:36959729 | DOI:10.1093/jxb/erad108

Chin Med J (Engl). 2023 Mar 24. doi: 10.1097/CM9.0000000000002421. Online ahead of print.ABSTRACTBACKGROUND: Type 2 diabetes mellitus (T2DM) is an independent risk factor for colorectal cancer (CRC), and the patients with CRC and T2DM have worse survival. The human gut microbiota (GM) is linked to the development of CRC and T2DM, respectively. However, the GM characteristics in patients with CRC and T2DM remain unclear.METHODS: We performed fecal metagenomic and targeted metabolomics studies on 36 samples from CRC patients with T2DM (DCRC group, n = 12), CRC patients without diabetes (CRC group, n = 12), and healthy controls (Health group, n = 12). We analyzed the fecal microbiomes, characterized the composition and function based on the metagenomics of DCRC patients, and detected the short-chain fatty acids (SCFAs) and bile acids (BAs) levels in all fecal samples. Finally, we performed a correlation analysis of the differential bacteria and metabolites between different groups.RESULTS: Compared with the CRC group, LefSe analysis showed that there is a specific GM community in DCRC group, including an increased abundance of Eggerthella, Hungatella, Peptostreptococcus, and Parvimonas, and decreased Butyricicoccus, Lactobacillus, and Paraprevotella. The metabolomics analysis results revealed that the butyric acid level was lower but the deoxycholic acid and 12-keto-lithocholic acid levels were higher in the DCRC group than other groups (P < 0.05). The correlation analysis showed that the dominant bacterial abundance in the DCRC group (Parvimonas, Desulfurispora, Sebaldella, and Veillonellales, among others) was negatively correlated with butyric acid, hyodeoxycholic acid, ursodeoxycholic acid, glycochenodeoxycholic acid, chenodeoxycholic acid, cholic acid and glycocholate. However, the abundance of mostly inferior bacteria was positively correlated with these metabolic acid levels, including Faecalibacterium, Thermococci, and Cellulophaga.CONCLUSIONS: Unique fecal microbiome signatures exist in CRC patients with T2DM compared to those with non-diabetic CRC. Alterations in GM composition and SCFAs and secondary BAs levels may promote CRC development.PMID:36959686 | DOI:10.1097/CM9.0000000000002421

Sci Rep. 2023 Mar 23;13(1):4747. doi: 10.1038/s41598-023-31429-7.ABSTRACTThis integrative study of transcriptomics and metabolomics aimed to improve our understanding of Wooden Breast myopathy (WB). Breast muscle samples from 8 WB affected and 8 unaffected male broiler chickens of 47 days of age were harvested for metabolite profiling. Among these 16 samples, 5 affected and 6 unaffected also underwent gene expression profiling. The Joint Pathway Analysis was applied on 119 metabolites and 3444 genes exhibiting differential abundance or expression between WB affected and unaffected chickens. Mitochondrial dysfunctions in WB was suggested by higher levels of monoacylglycerols and down-regulated genes involved in lipid production, fatty acid beta oxidation, and oxidative phosphorylation. Lower levels of carnosine and anserine, along with down-regulated carnosine synthase 1 suggested decreased carnosine synthesis and hence impaired antioxidant capacity in WB. Additionally, Weighted Gene Co-expression Network Analysis results indicated that abundance of inosine monophosphate, significantly lower in WB muscle, was correlated with mRNA expression levels of numerous genes related to focal adhesion, extracellular matrix and intercellular signaling, implying its function in connecting and possibly regulating multiple key biological pathways. Overall, this study showed not only the consistency between transcript and metabolite profiles, but also the potential in gaining further insights from analyzing multi-omics data.PMID:36959331 | DOI:10.1038/s41598-023-31429-7

J Mol Med (Berl). 2023 Mar 24. doi: 10.1007/s00109-023-02309-4. Online ahead of print.ABSTRACTEbola virus can trigger a release of pro-inflammatory cytokines with subsequent vascular leakage and impairment of clotting finally leading to multiorgan failure and shock after entering and infecting patients. Ebola virus is known to directly target endothelial cells and macrophages, even without infecting them, through direct interactions with viral proteins. These interactions affect cellular mechanics and immune processes, which are tightly linked to other key cellular functions such as metabolism. However, research regarding metabolic activity of these cells upon viral exposure remains limited, hampering our understanding of its pathophysiology and progression. Therefore, in the present study, an untargeted cellular metabolomic approach was performed to investigate the metabolic alterations of primary human endothelial cells and M1 and M2 macrophages upon exposure to Ebola virus-like particles (VLP). The results show that Ebola VLP led to metabolic changes among endothelial, M1, and M2 cells. Differential metabolite abundance and perturbed signaling pathway analysis further identified specific metabolic features, mainly in fatty acid-, steroid-, and amino acid-related metabolism pathways for all the three cell types, in a host cell specific manner. Taken together, this work characterized for the first time the metabolic alternations of endothelial cells and two primary human macrophage subtypes after Ebola VLP exposure, and identified the potential metabolites and pathways differentially affected, highlighting the important role of those host cells in disease development and progression. KEY MESSAGES: • Ebola VLP can lead to metabolic alternations in endothelial cells and M1 and M2 macrophages. • Differential abundance of metabolites, mainly including fatty acids and sterol lipids, was observed after Ebola VLP exposure. • Multiple fatty acid-, steroid-, and amino acid-related metabolism pathways were observed perturbed.PMID:36959259 | DOI:10.1007/s00109-023-02309-4

Sci Rep. 2023 Mar 23;13(1):4758. doi: 10.1038/s41598-023-31547-2.ABSTRACTInteractions between various molecular species in biological phenomena give rise to numerous networks. The investigation of these networks, including their statistical and biochemical interactions, supports a deeper understanding of biological phenomena. The clustering of nodes associated with molecular species and enrichment analysis is frequently applied to examine the biological significance of such network structures. However, these methods focus on delineating the function of a node. As such, in-depth investigations of the edges, which are the connections between the nodes, are rarely explored. In the current study, we aimed to investigate the functions of the edges rather than the nodes. To accomplish this, for each network, we categorized the edges and defined the edge type based on their biological annotations. Subsequently, we used the edge type to compare the network structures of the metabolome and transcriptome in the livers of healthy (wild-type) and obese (ob/ob) mice following oral glucose administration (OGTT). The findings demonstrate that the edge type can facilitate the characterization of the state of a network structure, thereby reducing the information available through datasets containing the OGTT response in the metabolome and transcriptome.PMID:36959243 | DOI:10.1038/s41598-023-31547-2

Cell Mol Bioeng. 2023 Mar 23;16(2):99-115. doi: 10.1007/s12195-023-00760-4. eCollection 2023 Apr.ABSTRACTBACKGROUND: Identification and quantitation of newly synthesized proteins (NSPs) are critical to understanding protein dynamics in development and disease. Probing the nascent proteome can be achieved using non-canonical amino acids (ncAAs) to selectively label the NSPs utilizing endogenous translation machinery, which can then be quantitated with mass spectrometry. We have previously demonstrated that labeling the in vivo murine proteome is feasible via injection of azidohomoalanine (Aha), an ncAA and methionine (Met) analog, without the need for Met depletion. Aha labeling can address biological questions wherein temporal protein dynamics are significant. However, accessing this temporal resolution requires a more complete understanding of Aha distribution kinetics in tissues.RESULTS: To address these gaps, we created a deterministic, compartmental model of the kinetic transport and incorporation of Aha in mice. Model results demonstrate the ability to predict Aha distribution and protein labeling in a variety of tissues and dosing paradigms. To establish the suitability of the method for in vivo studies, we investigated the impact of Aha administration on normal physiology by analyzing plasma and liver metabolomes following various Aha dosing regimens. We show that Aha administration induces minimal metabolic alterations in mice.CONCLUSIONS: Our results demonstrate that we can reproducibly predict protein labeling and that the administration of this analog does not significantly alter in vivo physiology over the course of our experimental study. We expect this model to be a useful tool to guide future experiments utilizing this technique to study proteomic responses to stimuli.SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12195-023-00760-4.PMID:37096070 | PMC:PMC10121978 | DOI:10.1007/s12195-023-00760-4

Proteomes. 2023 Mar 23;11(2):11. doi: 10.3390/proteomes11020011.ABSTRACTAlthough numerous studies support a dose-effect relationship between Endocrine disruptors (EDs) and the progression and malignancy of tumors, the impact of a chronic exposure to non-lethal concentrations of EDs in cancer remains unknown. More specifically, a number of studies have reported the impact of Aldrin on a variety of cancer types, including prostate cancer. In previous studies, we demonstrated the induction of the malignant phenotype in DU145 prostate cancer (PCa) cells after a chronic exposure to Aldrin (an ED). Proteins are pivotal in the regulation and control of a variety of cellular processes. However, the mechanisms responsible for the impact of ED on PCa and the role of proteins in this process are not yet well understood. Here, two complementary computational approaches have been employed to investigate the molecular processes underlying the acquisition of malignancy in prostate cancer. First, the metabolic reprogramming associated with the chronic exposure to Aldrin in DU145 cells was studied by integrating transcriptomics and metabolomics via constraint-based metabolic modeling. Second, gene set enrichment analysis was applied to determine (i) altered regulatory pathways and (ii) the correlation between changes in the transcriptomic profile of Aldrin-exposed cells and tumor progression in various types of cancer. Experimental validation confirmed predictions revealing a disruption in metabolic and regulatory pathways. This alteration results in the modification of protein levels crucial in regulating triacylglyceride/cholesterol, linked to the malignant phenotype observed in Aldrin-exposed cells.PMID:37092452 | DOI:10.3390/proteomes11020011

Gut. 2023 Mar 23:gutjnl-2022-328048. doi: 10.1136/gutjnl-2022-328048. Online ahead of print.ABSTRACTOBJECTIVE: Inflammatory bowel disease (IBD) is a multifactorial immune-mediated inflammatory disease of the intestine, comprising Crohn's disease and ulcerative colitis. By characterising metabolites in faeces, combined with faecal metagenomics, host genetics and clinical characteristics, we aimed to unravel metabolic alterations in IBD.DESIGN: We measured 1684 different faecal metabolites and 8 short-chain and branched-chain fatty acids in stool samples of 424 patients with IBD and 255 non-IBD controls. Regression analyses were used to compare concentrations of metabolites between cases and controls and determine the relationship between metabolites and each participant's lifestyle, clinical characteristics and gut microbiota composition. Moreover, genome-wide association analysis was conducted on faecal metabolite levels.RESULTS: We identified over 300 molecules that were differentially abundant in the faeces of patients with IBD. The ratio between a sphingolipid and L-urobilin could discriminate between IBD and non-IBD samples (AUC=0.85). We found changes in the bile acid pool in patients with dysbiotic microbial communities and a strong association between faecal metabolome and gut microbiota. For example, the abundance of Ruminococcus gnavus was positively associated with tryptamine levels. In addition, we found 158 associations between metabolites and dietary patterns, and polymorphisms near NAT2 strongly associated with coffee metabolism.CONCLUSION: In this large-scale analysis, we identified alterations in the metabolome of patients with IBD that are independent of commonly overlooked confounders such as diet and surgical history. Considering the influence of the microbiome on faecal metabolites, our results pave the way for future interventions targeting intestinal inflammation.PMID:36958817 | DOI:10.1136/gutjnl-2022-328048

J Lipid Res. 2023 Mar 21:100361. doi: 10.1016/j.jlr.2023.100361. Online ahead of print.ABSTRACTN-acyl taurines (NATs) are bioactive lipids with emerging roles in glucose homeostasis and lipid metabolism. The acyl-chains of hepatic and biliary NATs are enriched in poly-unsaturated fatty acids (PUFAs). Dietary supplementation with a class of PUFAs, the omega-3 fatty acids, increases their cognate NATs in mice and humans. However, the synthesis pathway of the PUFA-containing NATs remains undiscovered. Here, we report that human livers synthesize NATs and that the acyl-chain preference is similar in murine liver homogenates. In the mouse, we found that hepatic NAT synthase activity localizes to the peroxisome and depends upon an active-site cysteine. Using unbiased metabolomics and proteomics, we identified bile acid-CoA:amino acid N-acyltransferase (BAAT) as the likely hepatic NAT synthase in vitro. Subsequently, we confirmed that BAAT knockout livers lack up to 90% of NAT synthase activity and that biliary PUFA-containing NATs are significantly reduced compared to wildtype. In conclusion, we identified the in vivo PUFA-NAT synthase in the murine liver and expanded the known substrates of the bile acid-conjugating enzyme, BAAT, beyond classic bile acids to the synthesis of a novel class of bioactive lipids.PMID:36958721 | DOI:10.1016/j.jlr.2023.100361

J Ethnopharmacol. 2023 Mar 21:116395. doi: 10.1016/j.jep.2023.116395. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Curculigo orchioides Gaertn. (CO), a traditional Chinese herb recorded in Chinese Pharmacopoeia, can nourish kidney yang, strengthen bones, and dispell cold-dampness. Raw CO (rCO) and wine-processed CO (pCO), the main processed products of CO for clinical application, show differences in nourishing kidney yang and ameliorate osteoporosis. However, the difference in efficacy and mechanism of rCO and pCO on bone destruction in rheumatoid arthritis (RA) remain unclear.AIM OF THE STUDY: To compare the pharmacodynamics of rCO and pCO in the treatment of bone destruction in RA and to reveal the potential mechanism by which rCO and pCO exert effects by metabolomics approach.MATERIALS AND METHODS: Ultra-high performance liquid chromatography Q exactive mass spectrometry (UHPLC-Q-Exactive-MS) combined with multivariate data analysis was applied to identify the differential chemical components in rCO and pCO. Collagen-induced arthritis (CIA) rats were orally administrated with different doses of rCO and pCO for 4 weeks. The body weight, paw swelling, arthritis scores, serum inflammatory cytokines concentration, knee tumor necrosis factor (TNF)-α, interleukin (IL)-6 protein levels, and inflammatory cell infiltration were determined to investigate the effects of rCO and pCO on arthritic symptoms and inflammatory responses in CIA rats. The effects of rCO and pCO on bone destruction were assessed using safranin O-fast green and tartrate-resistant acid phosphatase (TRAP) staining, immunohistochemical analysis of osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) proteins, and micro-computed tomography (micro-CT) in rats. In addition, metabolomics was performed to explore the mechanism of rCO and pCO against bone destruction in RA.RESULTS: A total of 41 chemical constituents were identified in both rCO and pCO, 9 of which were screened out as discriminatory compounds. According to the pharmacodynamic assays, pCO exhibited a stronger effect than rCO in attenuating the severity of arthritis, reducing inflammation, and inhibiting bone destruction. The metabolomics results showed that pentose phosphate pathway was the key metabolic pathways regulated by rCO, while pCO regulated multiple metabolic pathways including phenylalanine metabolism pathways, phenylalanine, tyrosine and tryptophan biosynthesis, taurine and hypotaurine metabolism, and glycerophospholipid metabolism pathways.CONCLUSION: pCO displayed a better effect on alleviating bone destruction in RA was than rCO. This might be associated with that pCO can decrease inflammation in RA through regulating more metabolism pathways.PMID:36958673 | DOI:10.1016/j.jep.2023.116395

Clin Chim Acta. 2023 Mar 21:117304. doi: 10.1016/j.cca.2023.117304. Online ahead of print.ABSTRACTBACKGROUND: A rapid and accurate measurement approach for 17α-hydroxyprogesterone (17-OHP) and related steroids in amount/volume-limited clinic samples is of importance for precise newborn diagnosis of congenital adrenal hyperplasia (CAH) and its subtypes in clinic.METHODS: Sixteen steroids (17-OHP, androstenedione, cortisol, tetrahydro-11-deoxycortisol, pregnenolone, progesterone, 11-deoxycorticosterone, corticosterone, 21-deoxycortisol, 11-deoxycortisol, dehydroepiandrosterone, testosterone, aldosterone, 17α-hydroxypregnenolone, dihydrotestosterone and 18-hydroxycorticosterone) were included in the panel of high-throughput microbore ultra-performance liquid chromatography-tandem mass spectrometry. Samples were collected from 126 normal subjects and 65 patients including different subtypes of CAH.RESULTS: The method was validated with satisfactory analytical performance in linearity, repeatability, recovery and limit of detection. Reference intervals for 16 steroids were established by quantifying the level of steroids detected in normal infants. The applicability of the method was tested by differentiating steroid metabolic characteristics between normal infants and infants with CAH, as well as between infants with different CAH subtypes. The relevance of 17-OHP, 21-deoxycortisol, and 17-OHP/11-deoxycortisol for 21-hydroxylase deficiency screening was demonstrated. The level of 11-deoxycorticosterone, 11-deoxycortisol, progesterone and androstenedione can be used for the diagnosis of different rare subtypes of CAH.CONCLUSION: This study provides a strategy for highly efficient steroid analysis of amount/volume-limited clinic samples and holds great potential for clinical diagnosis of CAH.PMID:36958425 | DOI:10.1016/j.cca.2023.117304

Mol Metab. 2023 Mar 21:101711. doi: 10.1016/j.molmet.2023.101711. Online ahead of print.ABSTRACTHeart diseases are the leading cause of deaths worldwide. Metabolic interventions via ketogenic diets (KDs) have been used for decades to treat epilepsy, and more recently, also diabetes and obesity, as common comorbidities of heart diseases. However, recent reports linked KDs, based on long-chain triglycerides (LCTs), to cardiac fibrosis and a reduction of heart function in rodents. As intervention using medium-chain triglycerides (MCTs) was recently shown to be beneficial in murine cardiac reperfusion injury, the question arises as to what extent the fatty acid (FA)-composition in a KD alters molecular markers of FA-oxidation (FAO) and modulates cardiac fibrotic outcome. Here, we show that eight weeks of feeding an LCT-KD as well as an LCT/MCT mix (8:1 ketogenic ratio) induces cardiac fibrosis in male C57/BL6NRJ mice. Despite the increased amount of collagen fibers, cardiac tissue was immunologically indistinguishable between groups. MCT supplementation resulted in i) profound changes in plasma metabolome, ii) reduced hydroxymethylglutaryl-CoA synthase upregulation, and mitofusin 2 downregulation, iii) abrogation of LCT-induced mitochondrial enlargement, and iv) enhanced FAO profile. Contrary to literature, mitochondrial biogenesis was unaffected by KDs. We propose that the tissue remodeling, which we observed, is caused by the accumulation of 4-hydroxy-2-nonenal protein adducts, despite an inconspicuous nuclear factor (erythroid-derived 2)-like 2 pathway. We conclude that in spite of the generally favorable effects of MCTs, they cannot inhibit 4-hydroxy-2-nonenal adduct formation and fibrotic tissue formation in this setting. Furthermore, we support the burgeoning concern about the effect of KDs on the cardiac safety profile.PMID:36958422 | DOI:10.1016/j.molmet.2023.101711

J Nutr Biochem. 2023 Mar 21:109323. doi: 10.1016/j.jnutbio.2023.109323. Online ahead of print.ABSTRACTSelenium (Se) is a trace element crucial for human health. Recently, the impact of Se supplementation on gut microbiota has been pointed out as well as its influence on the expression of certain selenoproteins and gut metabolites. This study aims to elucidate the link between Se supplementation, brain selenoproteins and brain metabolome as well as the possible connection with the gut-brain axis. To this end, an in vivo study with 40 BALB/c mice was carried out. The study included conventional (n=20) and mice model with microbiota depleted by antibiotics (n=20) under a regular or Se supplemented diet. Brain selenoproteome was determined by a transcriptomic/gene expression profile, while brain metabolome and gut microbiota profiles were accomplished by untargeted metabolomics and amplicon sequencing, respectively. The total content of Se in brain was also determined. The selenoproteins genes Dio and Gpx isoenzymes, SelenoH, SelenoI, SelenoT, SelenoV and SelenoW and 31 metabolites were significantly altered in the brain after Se supplementation in conventional mice, while 11 selenoproteins and 26 metabolites were altered in microbiota depleted mice. The main altered brain metabolites were related to glyoxylate and dicarboxylate metabolism, amino acid metabolism, and gut microbiota that have been previously related with the gut-brain axis (e.g., members of Lachnospiraceae and Ruminococcaceae families). Moreover, specific associations were determined between brain selenoproteome and metabolome, which correlated with the same bacteria, suggesting an intertwined mechanism. Our results demonstrated the effect of Se on brain metabolome through specific selenoproteins gene expression and gut microbiota.PMID:36958417 | DOI:10.1016/j.jnutbio.2023.109323

J Photochem Photobiol B. 2023 Mar 11;242:112692. doi: 10.1016/j.jphotobiol.2023.112692. Online ahead of print.ABSTRACTLigusticum chuanxiong Hort. (Chuanxiong) is an important Chinese medicinal herb, whose rhizomes are widely used as raw materials for treating various diseases caused by blood stasis. The fresh tender stems and leaves of Chuanxiong are also consumed and have the potential as microgreens. Here, we investigated the effect of light spectra on yield and total flavonoid content of Chuanxiong microgreens by treatment with LED-based white light (WL), red light (RL), blue light (BL), and continuous darkness (DD). The results showed that WL and BL reduced biomass accumulation but significantly increased total flavonoid content compared to RL or DD treatments. Widely targeted metabolomics analysis confirmed that BL promoted the accumulation of flavones and flavonols in Chuanxiong microgreens. Further integration of transcriptomics and metabolomics analysis revealed the mechanism by which BL induces the up-regulation of transcription factors such as HY5 and MYBs, promotes the expression of key genes targeted for flavonoid biosynthesis, and ultimately leads to the accumulation of flavones and flavonols. This study suggests that blue light is a proper light spectra to improve the quality of Chuanxiong microgreens, and the research results lay a foundation for guiding the de-etiolation of Chuanxiong microgreens to obtain both yield and quality in production practice.PMID:36958087 | DOI:10.1016/j.jphotobiol.2023.112692