PubMed

Anim Nutr. 2022 Dec 31;13:50-63. doi: 10.1016/j.aninu.2022.12.006. eCollection 2023 Jun.ABSTRACTSince the aquaculture industry is currently observing a deterioration in the flesh quality of farmed fish, the use of nutrients as additives to improve the flesh quality of farmed fish species is a viable strategy. The aim of this study was to investigate the effect of dietary D-ribose (RI) on the nutritional value, texture and flavour of gibel carp (Carassius auratus gibelio). Four diets were formulated containing exogenous RI at 4 gradient levels: 0 (Control), 0.15% (0.15RI), 0.30% (0.30RI) and 0.45% (0.45RI). A total of 240 fish (150 ± 0.31 g) were randomly distributed into 12 fibreglass tanks (150 L per tank). Triplicate tanks were randomly assigned to each diet. The feeding trial was carried out in an indoor recirculating aquaculture system for 60 d. After the feeding trial, the muscle and liver of gibel carp were analysed. The results showed that RI supplementation did not result in any negative impact on the growth performance and 0.30RI supplementation significantly increased the whole-body protein content compared to the control group. The contents of collagen and glycogen in muscle were enhanced by RI supplementation. The alterations in the flesh indicated that RI supplementation improved the texture of the flesh in terms of its water-holding capacity and hardness, therefore improving the taste. Dietary RI facilitated the deposition of amino acids and fatty acids in the muscle that contributed to the meaty taste and nutritional value. Furthermore, a combination of metabolomics and expression of key genes in liver and muscle revealed that 0.30RI activated the purine metabolism pathways by supplementing the substrate for nucleotide synthesis and thereby promoting the deposition of flavour substance in flesh. This study offers a new approach for providing healthy, nutritious and flavourful aquatic products.PMID:37009072 | PMC:PMC10064418 | DOI:10.1016/j.aninu.2022.12.006

Food Chem X. 2023 Mar 14;18:100641. doi: 10.1016/j.fochx.2023.100641. eCollection 2023 Jun 30.ABSTRACTFlavor is a critical factor in apple quality. To better understand apple flavor, this study aimed to identify the relationships between sensory attributes and the chemical composition (volatiles and non-volatiles) of apples using a combined metabolomic and sensory evaluation. Sensory results showed the positive (apple, fruity, pineapple, sweetness, sourness) and negative (cucumber) flavor attributes of apples. A metabolomic analysis with statistical correlations revealed significant metabolites related to the flavor attributes of apples. Volatile esters (e.g., hexyl acetate and 2-methylbutyl acetate for apple and fruity notes) and non-volatile sugars and acids (total sugars, tartaric acid, and malic acid for balanced sweet and tart flavors) were associated with the apple flavor preferred by consumers. Some aldehydes and alcohols (e.g., (E)-2-nonenal) contributed to a negative hedonic perception (cucumber). The collected information demonstrated the roles of key chemical compounds in apple flavor quality, and may be applicable to quality control.PMID:37008726 | PMC:PMC10053392 | DOI:10.1016/j.fochx.2023.100641

Toxicol Res. 2023 Feb 14;39(2):307-315. doi: 10.1007/s43188-022-00167-9. eCollection 2023 Apr.ABSTRACTIn the environment, aquatic organisms are not only directly exposed to pollutants, but the effects can be exacerbated along the food chain. In this study, we investigated the effect of the food (water flea) on the secondary consumer (zebrafish) with the exposure diclofenac (DCF) Both organisms were exposed to an environmentally relevant concentrations (15 µg/L) of diclofenac for five days, and zebrafish were fed exposed and non-exposed water fleas, respectively. Metabolites of the water fleas were directly analyzed using HRMAS NMR, and for zebrafish, polar metabolite were extracted and analyzed using liquid NMR. Metabolic profiling was performed and statistically significant metabolites which affected by DCF exposure were identified. There were more than 20 metabolites with variable importance (VIP) score greater than 1.0 in comparisons in fish groups, and identified metabolites differed depending on the effect of exposure and the effect of food. Specifically, exposure to DCF significantly increased alanine and decreased NAD + in zebrafish, which means energy demand was increased. Additionally, the effects of exposed food decreased in guanosine, a neuroprotective metabolite, which explained that the neurometabolic pathway was perturbated by the feeding of exposed food. Our results which short-term exposed primary consumers to pollutants indirectly affected the metabolism of secondary consumers suggest that the long-term exposure further study remains to be investigated.PMID:37008688 | PMC:PMC10050267 | DOI:10.1007/s43188-022-00167-9

Front Plant Sci. 2023 Mar 16;14:1110623. doi: 10.3389/fpls.2023.1110623. eCollection 2023.ABSTRACTAs an essential agroforestry, intercropping legumes can improve the physical, chemical, and biological fertility of the soil in tea plantations. However, the effects of intercropping different legume species on soil properties, bacterial communities, and metabolites remain elusive. In this study, the 0-20 cm and 20-40 cm soils of three planting patterns (T1: tea plants/mung bean intercropping, T2: tea plants/adzuki bean intercropping, T3: tea plants/mung bean and adzuki bean intercropping) were sampled to explore the diversity of the bacterial community and soil metabolites. The findings showed that, as compared to monocropping, intercropping systems had greater concentrations of organic matter (OM) and dissolved organic carbon (DOC). Notably, pH values were significantly lower, and soil nutrients increased in intercropping systems compared with monoculture in 20-40 cm soils, especially in T3. In addition, intercropping resulted in an increased relative abundance of Proteobacteria but a decreased relative abundance of Actinobacteria. 4-methyl-Tetradecane, acetamide, and diethyl carbamic acid were key metabolites mediating the root-microbe interactions, especially in tea plants/adzuki intercropping and tea plants/mung bean, adzuki bean mixed intercropping soils. Co-occurrence network analysis showed that arabinofuranose, abundant in tea plants and adzuki bean intercropping soils, showed the most remarkable correlation with the soil bacterial taxa. Our findings demonstrate that intercropping with adzuki beans is better at enhancing the diversity of soil bacteria and soil metabolites and is more weed-suppressing than other tea plants/legume intercropping systems.PMID:37008505 | PMC:PMC10060988 | DOI:10.3389/fpls.2023.1110623

Front Plant Sci. 2023 Mar 16;14:1154088. doi: 10.3389/fpls.2023.1154088. eCollection 2023.ABSTRACTRoots are sensors evolved to simultaneously respond to manifold signals, which allow the plant to survive. Root growth responses, including the modulation of directional root growth, were shown to be differently regulated when the root is exposed to a combination of exogenous stimuli compared to an individual stress trigger. Several studies pointed especially to the impact of the negative phototropic response of roots, which interferes with the adaptation of directional root growth upon additional gravitropic, halotropic or mechanical triggers. This review will provide a general overview of known cellular, molecular and signalling mechanisms involved in directional root growth regulation upon exogenous stimuli. Furthermore, we summarise recent experimental approaches to dissect which root growth responses are regulated upon which individual trigger. Finally, we provide a general overview of how to implement the knowledge gained to improve plant breeding.PMID:37008498 | PMC:PMC10060999 | DOI:10.3389/fpls.2023.1154088

Front Plant Sci. 2023 Mar 16;14:1145418. doi: 10.3389/fpls.2023.1145418. eCollection 2023.ABSTRACTINTRODUCTION: Chestnut (Castanea mollissima BL.) is an important woody grain, and its flower formation has a significant impact on fruit yield and quality. Some chestnut species in northern China re-flower in the late summer. On the one hand, the second flowering consumes a lot of nutrients in the tree, weakening the tree and thus affecting flowering in the following year. On the other hand, the number of female flowers on a single bearing branch during the second flowering is significantly higher than that of the first flowering, which can bear fruit in bunches. Therefore, these can be used to study the sex differentiation of chestnut.METHODS: In this study, the transcriptomes, metabolomes, and phytohormones of male and female chestnut flowers were determined during spring and late summer. We aimed to understand the developmental differences between the first and secondary flowering stages in chestnuts. We analysed the reasons why the number of female flowers is higher in the secondary flowering than in the first flowering and found ways to increase the number of female flowers or decrease the number of male flowers in chestnuts.RESULTS: Transcriptome analysis of male and female flowers in different developmental seasons revealed that EREBP-like mainly affected the development of secondary female flowers and HSP20 mainly affected the development of secondary male flowers. KEGG enrichment analysis showed that 147 common differentially-regulated genes were mainly enriched from circadian rhythm-plant, carotenoid biosynthesis, phenylpropanoid biosynthesis, and plant hormone signal transduction pathways. Metabolome analysis showed that the main differentially accumulated metabolites in female flowers were flavonoids and phenolic acids, whereas the main differentially accumulated metabolites in male flowers were lipids, flavonoids, and phenolic acids. These genes and their metabolites are positively correlated with secondary flower formation. Phytohormone analysis showed that abscisic and salicylic acids were negatively correlated with secondary flower formation. MYB305, a candidate gene for sex differentiation in chestnuts, promoted the synthesis of flavonoid substances and thus increased the number of female flowers.DISCUSSION: We constructed a regulatory network for secondary flower development in chestnuts, which provides a theoretical basis for the reproductive development mechanism of chestnuts. This study has important practical implications for improving chestnut yield and quality.PMID:37008486 | PMC:PMC10060901 | DOI:10.3389/fpls.2023.1145418

Front Plant Sci. 2023 Mar 17;14:1142814. doi: 10.3389/fpls.2023.1142814. eCollection 2023.ABSTRACTINTRODUCTION: Buckwheat (Fagopyrum tataricum), an important food crop, also has medicinal uses. It is widely planted in Southwest China, overlapping with planting areas remarkably polluted by cadmium (Cd). Therefore, it is of great significance to study the response mechanism of buckwheat under Cd stress and further develop varieties with excellent Cd tolerance.METHODS: In this study, two critical periods of Cd stress treatment (days 7 and 14 after Cd treatment) of cultivated buckwheat (Pinku-1, named K33) and perennial species (F. tatari-cymosum Q.F. Chen) (duoku, named DK19) were analyzed using transcriptome and metabolomics.RESULTS: The results showed that Cd stress led to changes in reactive oxygen species (ROS) and the chlorophyll system. Moreover, Cd-response genes related to stress response, amino acid metabolism, and ROS scavenging were enriched or activated in DK19. Transcriptome and metabolomic analyses highlighted the important role of galactose, lipid (glycerophosphatide metabolism and glycerophosphatide metabolism), and glutathione metabolism in response to Cd stress in buckwheat, which are significantly enriched at the gene and metabolic levels in DK19.DISCUSSION: The results of the present study provide valuable information for a better understanding of the molecular mechanisms underlying Cd tolerance in buckwheat and useful clues for the genetic improvement of drought tolerance in buckwheat.PMID:37008482 | PMC:PMC10064074 | DOI:10.3389/fpls.2023.1142814

Front Plant Sci. 2023 Mar 15;14:1129114. doi: 10.3389/fpls.2023.1129114. eCollection 2023.ABSTRACTDrought is a common and serious abiotic stress in viticulture, and it is urgent to select effective measures to alleviate it. The new plant growth regulator 5-aminolevulinic acid (ALA) has been utilized to alleviate abiotic stresses in agriculture in recent years, which provided a novel idea to mitigate drought stress in viticulture. The leaves of 'Shine Muscat' grapevine (Vitis vinifera L.) seedlings were treated with drought (Dro), drought plus 5-aminolevulinic acid (ALA, 50 mg/L) (Dro_ALA) and normal watering (Control) to clarify the regulatory network used by ALA to alleviate drought stress in grapevine. Physiological indicators showed that ALA could effectively reduce the accumulation of malondialdehyde (MDA) and increase the activities of peroxidase (POD) and superoxide dismutase (SOD) in grapevine leaves under drought stress. At the end of treatment (day 16), the MDA content in Dro_ALA was reduced by 27.63% compared with that in Dro, while the activities of POD and SOD reached 2.97- and 5.09-fold of those in Dro, respectively. Furthermore, ALA reduces abscisic acid by upregulating CYP707A1, thus, relieving the closure of stomata under drought. The chlorophyll metabolic pathway and photosynthetic system are the major pathways affected by ALA to alleviate drought. Changes in the genes of chlorophyll synthesis, including CHLH, CHLD, POR, and DVR; genes related to degradation, such as CLH, SGR, PPH and PAO; the RCA gene that is related to Rubisco; and the genes AGT1 and GDCSP related to photorespiration form the basis of these pathways. In addition, the antioxidant system and osmotic regulation play important roles that enable ALA to maintain cell homeostasis under drought. The reduction of glutathione, ascorbic acid and betaine after the application of ALA confirmed the alleviation of drought. In summary, this study revealed the mechanism of effects of drought stress on grapevine, and the alleviating effect of ALA, which provides a new concept to alleviate drought stress in grapevine and other plants.PMID:37008472 | PMC:PMC10061586 | DOI:10.3389/fpls.2023.1129114

Front Plant Sci. 2023 Mar 17;14:1147076. doi: 10.3389/fpls.2023.1147076. eCollection 2023.ABSTRACTThe intercropping practice has been regarded as a practical land-use selection to improve the management benefits of Bletilla striata plantations. The reports about the variety of economic and functional traits of Bletilla pseudobulb under intercropping systems were limited. The present study investigated the variation of economic and functional traits of Bletilla pseudobulb under different intercropping systems (the deep-rooted intercropping system: B. striata - Cyclocarya paliurus, CB; and the shallow-rooted intercropping system: B. striata - Phyllostachys edulis, PB). The functional traits were analyzed through non-targeted metabolomics based on GC-MS. The results indicated that the PB intercropping system significantly decreased the yield of Bletilla pseudobulb while significantly increasing the total phenol and flavonoids compared with the control (CK). However, there were no significant differences in all economic traits between CB and CK. The functional traits among CB, PB, and CK were separated and exhibited significant differences. Under different intercropping systems, B. striata may adopt different functional strategies in response to interspecific competition. The functional node metabolites (D-galactose, cellobiose, raffinose, D-fructose, maltose, and D-ribose) were up-regulated in CB, while the functional node metabolites (L-valine, L-leucine, L-isoleucine, methionine, L-lysine, serine, D-glucose, cellobiose, trehalose, maltose, D-ribose, palatinose, raffinose, xylobiose, L-rhamnose, melezitose, and maltotriose) were up-regulated in PB. The correlation between economic and functional traits depends on the degree of environmental stress. Artificial neural network models (ANNs) accurately predicted the variation in economic traits via the combination of functional node metabolites in PB. The correlation analysis of environmental factors indicated that Ns (including TN, NH4 +-, and NO3 --), SRI (solar radiation intensity), and SOC were the main factors that affected the economic traits (yield, total phenol, and total flavonoids). TN, SRI, and SOC were the main factors affecting the functional traits of the Bletilla pseudobulb. These findings strengthen our understanding of the variation of economic and functional traits of Bletilla pseudobulb under intercropping and clarify the main limiting environmental factors under B. striata intercropping systems.PMID:37008465 | PMC:PMC10064063 | DOI:10.3389/fpls.2023.1147076

Front Vet Sci. 2023 Mar 16;10:1069809. doi: 10.3389/fvets.2023.1069809. eCollection 2023.ABSTRACTThe immune function of the intestinal mucosa plays a crucial role in the intestinal health of hosts. As signaling molecules and precursors of metabolic reactions, intestinal chyme metabolites are instrumental in maintaining host immune homeostasis. Saba (SB) pigs, a unique local pig species in central Yunnan Province, China. However, research on jejunal metabolites in this species is limited. Here, we used immunohistochemistry and untargeted metabolomics by liquid chromatography mass spectrometry (LC-MS/MS) to study differences in jejunal immunophenotypes and metabolites between six Landrace (LA) and six SB piglets (35 days old). The results showed that the levels of the anti-inflammatory factor interleukin 10 (IL-10) were markedly higher in SB piglets than in LA piglets (P < 0.01), while the levels of the proinflammatory factors IL-6, IL-1β, and Toll-like receptor 2 (TLR-2) were markedly lower (P < 0.01). Furthermore, the levels of mucin 2 (MUC2) and zona occludens (ZO-1), which are related to mucosal barrier function, were significantly higher in SB piglets than in LA piglets (P < 0.01), as were villus height, villus height/crypt depth ratio, and goblet cell number (P < 0.05). Differences in jejunal chyme metabolic patterns were observed between the two piglets. In the negative ion mode, cholic acid metabolites ranked in the top 20 and represented 25% of the total. Taurodeoxycholic acid (TDCA) content was significantly higher in SB piglets than in LA piglets (P < 0.01). TDCA positively correlated with ZO-1, villus height, villus height/crypt depth ratio, and goblet cell number. These results suggest that SB pigs have a strong jejunal immune function and that TDCA was positively regulates jejunal immunity and mucosal barrier function. Our findings provide a reference for understanding intestinal immune function in different pig breeds and for the discovery of potential biomarkers to help solve health issues related to pig production.PMID:37008364 | PMC:PMC10060822 | DOI:10.3389/fvets.2023.1069809

ACS Omega. 2023 Mar 20;8(12):11138-11150. doi: 10.1021/acsomega.2c07959. eCollection 2023 Mar 28.ABSTRACTThe Simiao pill (SMP) is a classic prescription that has shown anti-inflammatory, analgesic, and immunomodulatory effects and is clinically used to treat inflammatory diseases, such as rheumatoid arthritis (RA) and gouty arthritis, for which the effects and mechanism of action remain largely unknown. In this study, serum samples from RA rats were analyzed using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry based metabolomics technology and liquid chromatography with tandem mass spectrometry proteomics technology together with network pharmacology to explore the pharmacodynamic substances of SMP. To further verify the above results, we constructed a fibroblast-like synoviocyte (FLS) cell model and administered phellodendrine for the test. All these clues suggested that SMP can significantly reduce the level of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in complete Freund's adjuvant rat serum and improve the degree of foot swelling; combined with metabolomics, proteomics, and network pharmacological technology, it is determined that SMP plays a therapeutic role through the inflammatory pathway, and phellodendrine is found to be one of the pharmacodynamic substances. By constructing an FLS model, it is further determined that phellodendrine could effectively inhibit the activity of synovial cells and reduce the expression level of inflammatory factors by downregulating the expression level of related proteins in the TLR4-MyD88-IRAK4-MAPK signal pathway to alleviate joint inflammation and cartilage injury. Overall, these findings suggested that phellodendrine is an effective component of SMP in the treatment of RA.PMID:37008152 | PMC:PMC10061593 | DOI:10.1021/acsomega.2c07959

Front Neurol. 2023 Mar 16;13:1109019. doi: 10.3389/fneur.2022.1109019. eCollection 2022.ABSTRACTINTRODUCTION: Screening for metabolically relevant differentially expressed genes (DEGs) shared by hepatocellular carcinoma (HCC) and vascular cognitive impairment (VCI) to explore the possible mechanisms of HCC-induced VCI.METHODS: Based on metabolomic and gene expression data for HCC and VCI, 14 genes were identified as being associated with changes in HCC metabolites, and 71 genes were associated with changes in VCI metabolites. Multi-omics analysis was used to screen 360 DEGs associated with HCC metabolism and 63 DEGs associated with VCI metabolism.RESULTS: According to the Cancer Genome Atlas (TCGA) database, 882 HCC-associated DEGs were identified and 343 VCI-associated DEGs were identified. Eight genes were found at the intersection of these two gene sets: NNMT, PHGDH, NR1I2, CYP2J2, PON1, APOC2, CCL2, and SOCS3. The HCC metabolomics prognostic model was constructed and proved to have a good prognostic effect. The HCC metabolomics prognostic model was constructed and proved to have a good prognostic effect. Following principal component analyses (PCA), functional enrichment analyses, immune function analyses, and TMB analyses, these eight DEGs were identified as possibly affecting HCC-induced VCI and the immune microenvironment. As well as gene expression and gene set enrichment analyses (GSEA), a potential drug screen was conducted to investigate the possible mechanisms involved in HCC-induced VCI. The drug screening revealed the potential clinical efficacy of A-443654, A-770041, AP-24534, BI-2536, BMS- 509744, CGP-60474, and CGP-082996.CONCLUSION: HCC-associated metabolic DEGs may influence the development of VCI in HCC patients.PMID:37008043 | PMC:PMC10062391 | DOI:10.3389/fneur.2022.1109019

Front Physiol. 2023 Mar 16;14:1164926. doi: 10.3389/fphys.2023.1164926. eCollection 2023.ABSTRACTIntroduction: Eicosanoids are bioactive lipids present in packed red blood cells (PRBCs), and might play a role in transfusion-related immunomodulation (TRIM). We tested the feasibility of analyzing eicosanoid profiles in PRBC supernatant and in plasma samples of postoperative intensive care unit (ICU) patients transfused with one unit of PRBCs. Methods: We conducted a prospective, observational feasibility study enrolling postoperative ICU patients: 1) patients treated with acetylsalicylic acid following abdominal aortic surgery (Aorta); 2) patients on immunosuppressants after bilateral lung transplantation (LuTx); and 3) patients undergoing other types of major surgery (Comparison). Abundances of arachidonic acid (AA) and seven pre-defined eicosanoids were assessed by liquid chromatography and tandem mass spectrometry. PRBC supernatant was sampled directly from the unit immediately prior to transfusion. Spearman's correlations between eicosanoid abundance in PRBCs and storage duration were assessed. Patient plasma was collected at 30-min intervals: Three times each before and after transfusion. To investigate temporal changes in eicosanoid abundances, we fitted linear mixed models. Results: Of 128 patients screened, 21 were included in the final analysis (Aorta n = 4, LuTx n = 8, Comparison n = 9). In total, 21 PRBC and 125 plasma samples were analyzed. Except for 20-hydroxyeicosatetraenoic acid (HETE), all analyzed eicosanoids were detectable in PRBCs, and their abundance positively correlated with storage duration of PRBCs. While 5-HETE, 12-HETE/8-HETE, 15-HETE, 20-HETE, and AA were detectable in virtually all plasma samples, 9-HETE and 11-HETE were detectable in only 57% and 23% of plasma samples, respectively. Conclusions: Recruitment of ICU patients into this transfusion study was challenging but feasible. Eicosanoid abundances increased in PRBC supernatants during storage. In plasma of ICU patients, eicosanoid abundances were ubiquitously detectable and showed limited fluctuations over time prior to transfusion. Taken together, larger clinical studies seem warranted and feasible to further investigate the role of PRBC-derived eicosanoids in TRIM.PMID:37008004 | PMC:PMC10060532 | DOI:10.3389/fphys.2023.1164926

Front Physiol. 2023 Mar 16;14:1130861. doi: 10.3389/fphys.2023.1130861. eCollection 2023.ABSTRACTPost-traumatic stress disorder (PTSD) is a mental health disorder that arises after experiencing or witnessing a traumatic event. Despite affecting around 7% of the population, there are currently no definitive biological signatures or biomarkers used in the diagnosis of PTSD. Thus, the search for clinically relevant and reproducible biomarkers has been a major focus of the field. With significant advances of large-scale multi-omic studies that include genomic, proteomic, and metabolomic data, promising findings have been made, but the field still has fallen short. Amongst the possible biomarkers examined, one area is often overlooked, understudied, or inappropriately investigated: the field of redox biology. Redox molecules are free radical and/or reactive species that are generated as a consequence of the necessity of electron movement for life. These reactive molecules, too, are essential for life, but in excess are denoted as "oxidative stress" and often associated with many diseases. The few studies that have examined redox biology parameters have often utilized outdated and nonspecific methods, as well as have reported confounding results, which has made it difficult to conclude the role for redox in PTSD. Herein, we provide a foundation of how redox biology may underlie diseases like PTSD, critically examine redox studies of PTSD, and provide future directions the field can implement to enhance standardization, reproducibility, and accuracy of redox assessments for the use of diagnosis, prognosis, and therapy of this debilitating mental health disorder.PMID:37007993 | PMC:PMC10060537 | DOI:10.3389/fphys.2023.1130861

Front Physiol. 2023 Mar 13;14:1151268. doi: 10.3389/fphys.2023.1151268. eCollection 2023.ABSTRACTIntroduction: Exercise intolerance is a common clinical manifestation in patients with sickle cell disease (SCD), though the mechanisms are incompletely understood. Methods: Here we leverage a murine mouse model of sickle cell disease, the Berkeley mouse, to characterize response to exercise via determination of critical speed (CS), a functional measurement of mouse running speed upon exerting to exhaustion. Results: Upon observing a wide distribution in critical speed phenotypes, we systematically determined metabolic aberrations in plasma and organs-including heart, kidney, liver, lung, and spleen-from mice ranked based on critical speed performances (top vs. bottom 25%). Results indicated clear signatures of systemic and organ-specific alterations in carboxylic acids, sphingosine 1-phosphate and acylcarnitine metabolism. Metabolites in these pathways showed significant correlations with critical speed across all matrices. Findings from murine models were thus further validated in 433 sickle cell disease patients (SS genotype). Metabolomics analyses of plasma from 281 subjects in this cohort (with HbA < 10% to decrease confounding effects of recent transfusion events) were used to identify metabolic correlates to sub-maximal exercise test performances, as measure by 6 min walking test in this clinical cohort. Results confirmed strong correlation between test performances and dysregulated levels of circulating carboxylic acids (especially succinate) and sphingosine 1-phosphate. Discussion: We identified novel circulating metabolic markers of exercise intolerance in mouse models of sickle cell disease and sickle cell patients.PMID:37007990 | PMC:PMC10053510 | DOI:10.3389/fphys.2023.1151268

Front Genet. 2023 Mar 16;14:1141201. doi: 10.3389/fgene.2023.1141201. eCollection 2023.ABSTRACTThe causal agent of rust, Uromyces appendiculatus is a major constraint for common bean (Phaseolus vulgaris) production. This pathogen causes substantial yield losses in many common bean production areas worldwide. U. appendiculatus is widely distributed and although there have been numerous breakthroughs in breeding for resistance, its ability to mutate and evolve still poses a major threat to common bean production. An understanding of plant phytochemical properties can aid in accelerating breeding for rust resistance. In this study, metabolome profiles of two common bean genotypes Teebus-RR-1 (resistant) and Golden Gate Wax (susceptible) were investigated for their response to U. appendiculatus races (1 and 3) at 14- and 21-days post-infection (dpi) using liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (LC-qTOF-MS). Non-targeted data analysis revealed 71 known metabolites that were putatively annotated, and a total of 33 were statistically significant. Key metabolites including flavonoids, terpenoids, alkaloids and lipids were found to be incited by rust infections in both genotypes. Resistant genotype as compared to the susceptible genotype differentially enriched metabolites including aconifine, D-sucrose, galangin, rutarin and others as a defence mechanism against the rust pathogen. The results suggest that timely response to pathogen attack by signalling the production of specific metabolites can be used as a strategy to understand plant defence. This is the first study to illustrate the utilization of metabolomics to understand the interaction of common bean with rust.PMID:37007949 | PMC:PMC10060544 | DOI:10.3389/fgene.2023.1141201

Clin Kidney J. 2022 Dec 8;16(4):711-721. doi: 10.1093/ckj/sfac262. eCollection 2023 Apr.ABSTRACTBACKGROUND: Acute kidney injury (AKI) is often iatrogenic and potentially preventable. Reduced renal nicotinamide adenine dinucleotide (NAD+) is reported to increase the susceptibility of AKI. The present study explored the predictive value of urinary de novo NAD+ synthetic metabolites for AKI using two independent cohorts.METHODS: The expression of de novo NAD+ synthetic enzymes in human kidney was examined by immunohistochemistry and single-cell transcriptomes. Urine samples were collected from two independent cohorts: the methotrexate (MTX) cohort with high-dose MTX treatment for lymphoma (n = 189) and the liver transplantation cohort with orthotopic liver transplantation (n = 49). Urinary metabolomics study of NAD+ de novo synthesis was performed by liquid chromatography with mass spectrometry, screening for AKI predictive biomarkers. Nephroseq database and immunohistochemistry were used to analyze kidney de novo NAD+ synthetic enzymes expression in AKI-susceptible conditions.RESULTS: Human proximal tubule was the main structure in the kidney that expressed the necessary enzymes for NAD+ de novo synthesis. In the MTX cohort, the urinary quinolinic acid (QA)/3-hydroxyanthranilic acid (3-OH AA) ratio before chemotherapy was significantly lower in those who developed AKI after chemotherapy compared with those who did not. This finding was consistent in the liver transplantation cohort. The area under the receiver-operating characteristic curve (AUC) of urinary QA/3-OH AA for AKI prediction was 0.749 and 0.729 in two cohorts, respectively. 3-Hydroxyanthranilic acid dioxygenase (HAAO), the enzyme catalyzing QA synthesis from 3-OH AA, decreased in AKI-susceptible diabetic kidneys.CONCLUSIONS: The human proximal tubules were important source of NAD+ from the de novo pathway. Reduced urinary QA/3-OH AA ratio, which possibly suggested decreased HAAO activity, could be a potential AKI predictive biomarker.PMID:37007695 | PMC:PMC10061430 | DOI:10.1093/ckj/sfac262

Ann Transl Med. 2023 Mar 15;11(5):213. doi: 10.21037/atm-23-1074.ABSTRACTBACKGROUND: In previous studies, we found that smoking may participate in the pathogenesis of rheumatoid arthritis (RA) via the aryl hydrocarbon receptor (AhR) pathway. However, when we conducted a subgroup analysis, the expression of AhR and CYP1A1 in healthy people was higher than that in RA patients. We considered that endogenous AhR ligands may exist in vivo that activate AhR to play a protective role. Indole-3-pyruvic acid (IPA) is a tryptophan (Trp) metabolite produced by the indole pathway and serves as a ligand of AhR. This study aimed to reveal the effect and mechanism of IPA in RA.METHODS: A total of 14 patients with RA and 14 healthy volunteers were enrolled. The differential metabolites were screened with liquid chromatography-mass spectrometry (LC-MS) metabolomics technology. We also treated peripheral blood mononuclear cells (PBMCs) with IPA to evaluate the effect on the differentiation of T helper 17 (Th17) cells or regulatory T (Treg) cells. To determine whether IPA can be used to alleviate RA, we administered IPA to rats with collagen-induced arthritis (CIA). Methotrexate was used as a standard drug for CIA.RESULTS: When the dose reached 20 mg/kg/d, the severity of CIA was significantly reduced. In vitro experiments verified that IPA inhibited the differentiation of Th17 cells and promoted the differentiation of Treg cells, but this effect was weakened by CH223191.CONCLUSIONS: IPA is a protective factor for RA; it can restore the Th17/Treg cell balance through the AhR pathway, which can alleviate RA.PMID:37007545 | PMC:PMC10061485 | DOI:10.21037/atm-23-1074

Front Microbiol. 2023 Mar 15;14:1119981. doi: 10.3389/fmicb.2023.1119981. eCollection 2023.ABSTRACTPURPOSE: We aimed to explore the value of gut microbiota and tricarboxylic acid (TCA) metabolites in early diagnosis of necrotizing enterocolitis (NEC) among infants with abdominal manifestations.METHODS: Thirty-two preterm infants with abdominal manifestations at gestational age ≤ 34 weeks were included in the study and were divided into non-NEC (n = 16) and NEC (n = 16) groups. Faecal samples were collected when the infants were enrolled. The gut microbiota was analysed with high-throughput sequencing, and TCA metabolites were measured with multiple reaction monitoring (MRM) targeted metabolomics. Receiver operating characteristic (ROC) curves were generated to explore the predictive value of the obtained data.RESULTS: There was no significant difference in alpha diversity or beta diversity between the two groups (p > 0.05). At the phylum level, Proteobacteria increased, and Actinomycetota decreased in the NEC group (p < 0.05). At the genus level, Bifidobacterium and Lactobacillaceae decreased significantly, and at the species level, unclassified Staphylococcus, Lactobacillaceae and Bifidobacterium animalis subsp. lactis decreased in the NEC group (p < 0.05). Further Linear discriminant analysis effect sizes (LEfSe) analysis showed that the change in Proteobacteria at the phylum level and Lactobacillaceae and Bifidobacterium at the genus level scored higher than 4. The concentrations of succinate, L-malic acid and oxaloacetate in the NEC group significantly increased (p < 0.05), and the areas under the ROC curve for these metabolites were 0.6641, 0.7617, and 0.7344, respectively.CONCLUSION: Decreased unclassified Staphylococcus, Lactobacillaceae and Bifidobacterium animalis subsp. lactis at the species level as well as the increase in the contents of some TCA metabolites, including succinate, L-malic acid and oxaloacetate, have potential value for the early diagnosis of NEC.PMID:37007499 | PMC:PMC10050441 | DOI:10.3389/fmicb.2023.1119981

Front Microbiol. 2023 Mar 16;14:1138903. doi: 10.3389/fmicb.2023.1138903. eCollection 2023.ABSTRACTNecrotic enteritis (NE), especially subclinical NE (SNE), without clinical symptoms, in chicks has become one of the most threatening problems to the poultry industry. Therefore, increasing attention has been focused on the research and application of effective probiotic strains as an alternative to antibiotics to prevent SNE in broilers. In the present study, we evaluated the effects of Bacillus subtilis DSM29784 (BS) on the prevention of subclinical necrotic enteritis (SNE) in broilers. A total of 480 1-day-old broiler chickens were randomly assigned to four dietary treatments, each with six replicates pens of twenty birds for 63 d. The negative (Ctr group) and positive (SNE group) groups were only fed a basal diet, while the two treatment groups received basal diets supplemented with BS (1 × 109 colony-forming units BS/kg) (BS group) and 10mg/kg enramycin (ER group), respectively. On days 15, birds except those in the Ctr group were challenged with 20-fold dose coccidiosis vaccine, and then with 1 ml of C. perfringens (2 × 108) at days 18 to 21 for SNE induction. BS, similar to ER, effectively attenuated CP-induced poor growth performance. Moreover, BS pretreatment increased villi height, claudin-1 expression, maltase activity, and immunoglobulin abundance, while decreasing lesional scores, as well as mucosal IFN-γ and TNF-α concentrations. In addition, BS pretreatment increased the relative abundance of beneficial bacteria and decreased that of pathogenic species; many lipid metabolites were enriched in the cecum of treated chickens. These results suggest that BS potentially provides active ingredients that may serve as an antibiotic substitute, effectively preventing SNE-induced growth decline by enhancing intestinal health in broilers.PMID:37007491 | PMC:PMC10060821 | DOI:10.3389/fmicb.2023.1138903