PubMed

Int J Biol Macromol. 2023 Aug 15:126365. doi: 10.1016/j.ijbiomac.2023.126365. Online ahead of print.ABSTRACTGrain shape and plumpness affect barley yield. Despite numerous studies on shrunken endosperm mutants in barley, their molecular mechanism and application potential in the food industry are largely unknown. Here, map-based cloning, co-segregation analyses, and allelic variant validation revealed that the loss of HORVU6Hr1G037950 encoding an ADP-glucose transporter caused the shrunken endosperm in sex1. Haplotype analysis suggested that hap4 in the promoter sequence was positively related to the hundred-grain weight showing a breeding potential. A pair of near-isogenic lines targeting HORVU6Hr1G037950 was produced and characterized to investigate molecular mechanisms that SEX1 regulates endosperm development. Results presented that the absence of the SEX1 gene led to the decrease of starch content and A-type granules size, the increase of β-glucan, protein, gelatinization temperature, soluble sugar content, amylopectin A chains, and B1 chains. Enzymatic activity, transcriptome and metabolome analyses revealed the loss of SEX1 results in an impaired ADP-glucose-to-starch conversion process, consequently leading to higher soluble sugar contents and lower starch accumulation, thereby inducing a shrunken-endosperm phenotype in sex1. Taken together, this study provides new insights into barley grain development, and the elevated protein and β-glucan contents of the whole meal in sex1 imply its promising application in the food industry.PMID:37591421 | DOI:10.1016/j.ijbiomac.2023.126365

Environ Pollut. 2023 Aug 15:122387. doi: 10.1016/j.envpol.2023.122387. Online ahead of print.ABSTRACTPersistent organic pollutants (POPs) accumulated in the adipose tissue can affect the fatty acid and lipid metabolism in the body. Gas chromatography-mass spectrometry (GC-MS) metabolomics analysis was carried out to study the metabolic changes induced by internal exposure to the POPs in mouse skeletal muscle (soleus, plantaris, and gastrocnemius), kidney, heart, and lungs. Male donor mice were injected with a mixture of 10 POPs at concentrations of 0 × and 5 × lowest-observed-adverse-effect level (LOAEL). Their adipose tissue (AT) containing the POP was then grafted onto the host mice and the metabolic change of the host mice was monitored for 3 or 21 days. The metabolites related to fatty acid and lipid metabolism were studied. For the host mice engrafted with POP-containing fat pad, there was dysregulation of the fatty acids and glycerides observed in all the organs studied 3 days after the graft. However, there was no longer a significant change in the metabolites 21 days after the graft. The difference in significant values and metabolite regulation in each of the skeletal muscles showed that the POP mixture affects different types of skeletal muscle in a heterogeneous manner. Fold change analysis showed that certain metabolites in the kidney of host mice exposed to POPs for 3 days were greatly affected. Using multivariate analysis, apart from the plantaris, most treated groups exposed to POPs for 3 days are well distinguished from the control groups. However, for host mice exposed to POPs for 21 days, apart from the kidney and heart, groups are not well-distinguished from the control group. This study helps bring new insight into the effects of the pollutants mixture released from AT on fatty acid and lipid metabolism at different periods and how the dysregulation of metabolites might result in diseases associated with the organs.PMID:37591324 | DOI:10.1016/j.envpol.2023.122387

J Hazard Mater. 2023 Aug 14;459:132280. doi: 10.1016/j.jhazmat.2023.132280. Online ahead of print.ABSTRACTCadmium (Cd) contamination poses serious risks to soil ecosystems and human health. Herein, the effect of two drunken horse grasses (Achnatherum inebrians) including endophytes Epichloë gansuensis infected (E+ ) and uninfected (E-) on the phytoremediation of Cd-contaminated soils were analyzed by coupling high-throughput sequencing and soil metabolomics. The results showed that the high-risk soil Cd decreased and the medium- and low-risk Cd fraction increased to varying degrees after planting E+ and E- plants in the soil. Meanwhile, total Cd content decreased by 19.7 % and 35.1 % in E+ and E- A. inebrians-planted soils, respectively. Principal coordinate analysis revealed a significant impact of E+ and E- plants on the soil microbial community. Most stress-tolerant and gram-positive functional bacterial taxa were enriched to stabilize Cd(II) in E+ planted soil. Several beneficial fungal groups related to saprotroph and symbiotroph were enriched to absorb Cd(II) in E- soil. Soil metabolomic analysis showed that the introduction of A. inebrians could weaken the threat of CdCl2 to soil microbe metabolism and improve soil quality, which in turn promoted plant growth and improved phytoremediation efficiency in Cd-contaminated soil. In conclusion, A. inebrians plants alleviate soil Cd pollution by regulating soil microbial metabolism and microbial community structure. These results provide valuable information for an in-depth understanding of the phytoremediation mechanisms of A. inebrians.PMID:37591168 | DOI:10.1016/j.jhazmat.2023.132280

Comp Biochem Physiol Part D Genomics Proteomics. 2023 Aug 11;47:101117. doi: 10.1016/j.cbd.2023.101117. Online ahead of print.ABSTRACTThe sea cucumber Holothuria leucospilota, a nutritive and commercial marine species, has a high protein and low lipid content. To date, the mechanisms underlying gender determination and differentiation in sea cucumbers remain unclear. Identifying gender-specific molecular markers is an effective method of revealing the genetic basis of gender determination and differentiation. The inability to distinguish between male and female individuals causes reproductive efficiency to decline in aquaculture. In this study, we used the gonads of the sea cucumber H. leucospilota as samples to conduct the experiment. The differentially abundant metabolites (DAMs) detected by liquid chromatography-mass spectrometry were enriched in pathways associated with prolactin metabolism, insulin metabolism, hypoxia-inducible factor-1 signaling, and calcium signaling. At the transcriptome level, Illumina sequencing was performed on H. leucospilota, demonstrating that gender-specific expression genes were enriched in the retinoic acid-inducible gene I-like receptor signaling pathway, C-type lectin receptor signaling pathway, alpha-linolenic acid metabolism, and ether lipid metabolism by the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. By analyzing the common pathways between DAMs and differentially expressed genes, we found that gender-related genes of H. leucospilota were mostly enriched in the necroptosis pathway and the cysteine and methionine metabolism pathways. According to the common pathways, uch-sc1 and uch-sc2 are male-specific expression genes, and uch-sc3 and bhmt are female-specific expression genes at the mRNA level. These results provide information on gender differences in H. leucospilota.PMID:37591053 | DOI:10.1016/j.cbd.2023.101117

Chin Med. 2023 Aug 17;18(1):102. doi: 10.1186/s13020-023-00793-x.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Psoralea corylifolia Linn. (BGZ) is a commonly used traditional Chinese medicine (TCM) for the treatment of kidney-yang deficiency syndrome (Yangsyn) with good curative effect and security. However, BGZ was also reported to induce liver injury in recent years. According to TCM theory, taking BGZ may induce a series of adverse reactions in patients with kidney-yin deficiency syndrome (Yinsyn), which suggests that BGZ-induced liver damage may be related to its unreasonable clinical use.AIM OF THE STUDY: Liver injury caused by TCM is a rare but potentially serious adverse drug reaction, and the identification of predisposed individuals for drug-induced liver injury (DILI) remains challenging. The study aimed to investigate the differential responses to BGZ in Yangsyn and Yinsyn rat models and identify the corresponding characteristic biomarkers.MATERIALS AND METHODS: The corresponding animal models of Yangsyn and Yinsyn were induced by hydrocortisone and thyroxine + reserpine respectively. Body weight, organ index, serum biochemistry, and Hematoxylin and Eosin (HE) staining were used to evaluate the liver toxicity effect of BGZ on rats with Yangsyn and Yinsyn. Transcriptomics and metabonomics were used to screen the representative biomarkers (including metabolites and differentially expressed genes (DEGs)) changed by BGZ in Yangsyn and Yinsyn rats, respectively.RESULTS: The level changes of liver organ index, alanine aminotransferase (ALT), and aspartate aminotransferase (AST), suggested that BGZ has liver-protective and liver-damaging effects on Yangsyn and Yinsyn rats, respectively, and the results also were confirmed by the pathological changes of liver tissue. The results showed that 102 DEGs and 27 metabolites were significantly regulated related to BGZ's protective effect on Yangsyn, which is mainly associated with the glycerophospholipid metabolism, arachidonic acid metabolism, pantothenate, and coenzyme A (CoA) biosynthesis pathways. While 28 DEGs and 31 metabolites, related to the pathway of pantothenate and CoA biosynthesis, were significantly regulated for the BGZ-induced liver injury in Yinsyn. Furthermore, 4 DEGs (aldehyde dehydrogenase 1 family member B1 (Aldh1b1), solute carrier family 25 member 25 (Slc25a25), Pim-3 proto-oncogene, serine/threonine kinase (Pim3), out at first homolog (Oaf)) and 4 metabolites (phosphatidate, phosphatidylcholine, N-Acetylleucine, biliverdin) in the Yangsyn group and 1 DEG [galectin 5 (Lgals5)] and 1 metabolite (5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate) in Yinsyn group were significantly correlated to the ALT and AST levels of BGZ treated and untreated groups (receiver operating characteristic (ROC) ≥ 0.9).CONCLUSIONS: Yinsyn and Yangsyn are the predisposed syndromes for BGZ to exert liver damage and liver protection respectively, which are mainly related to the regulation of amino acid metabolism, lipid metabolism, energy metabolism, and metabolism of cofactors and vitamins. The results further suggest that attention should be paid to the selection of predisposed populations when using drugs related to the regulation of energy metabolism, and the Yinsyn/Yangsyn animal models based on the theory of TCM syndromes may be a feasible method for identifying the susceptible population to receive TCM.PMID:37592331 | DOI:10.1186/s13020-023-00793-x

J Transl Med. 2023 Aug 18;21(1):554. doi: 10.1186/s12967-023-04392-0.ABSTRACTBACKGROUND & AIMS: Intestinal fibrosis is a common and severe complication of inflammatory bowel disease without clear pathogenesis. Abnormal expression of host genes and metabolic perturbations might associate with the onset of intestinal fibrosis. In this study, we aimed to investigate the relationship between the development of intestinal fibrosis and the dynamic alterations in both fecal metabolites and host gene expression.METHODS: We induced intestinal fibrosis in a murine model using 2,4,6-trinitrobenzene sulfonic acid (TNBS). TNBS-treated or control mice were sacrificed after 4 and 6 weeks of intervention; alterations in colonic genes and fecal metabolites were determined by transcriptomics and metabolomics, respectively. Differential, tendency, enrichment, and correlation analyses were performed to assess the relationship between host genes and fecal metabolites.RESULTS: RNA-sequencing analysis revealed that 679 differential genes with enduring changes were mainly enriched in immune response-related signaling pathways and metabolism-related biological processes. Among them, 15 lipid metabolism-related genes were closely related to the development of intestinal fibrosis. Moreover, the fecal metabolic profile was significantly altered during intestinal fibrosis development, especially the lipid metabolites. Particularly, dynamic perturbations in lipids were strongly associated with alterations in lipid metabolism-related genes expression. Additionally, six dynamically altered metabolites might serve as biomarkers to identify colitis-related intestinal fibrosis in the murine model.CONCLUSIONS: Intestinal fibrosis in colitis mice might be related to dynamic changes in gene expression and metabolites. These findings could provide new insights into the pathogenesis of intestinal fibrosis.PMID:37592304 | DOI:10.1186/s12967-023-04392-0

BMC Biol. 2023 Aug 17;21(1):176. doi: 10.1186/s12915-023-01670-7.ABSTRACTBACKGROUND: Lotus corniculatus is a widely distributed perennial legume whose great adaptability to different environments and resistance to barrenness make it an excellent forage and ecological restoration plant. However, its molecular genetics and genomic relationships among populations are yet to be uncovered.RESULT: Here we report on a genomic variation map from worldwide 272 L. corniculatus accessions by genome resequencing. Our analysis suggests that L. corniculatus accessions have high genetic diversity and could be further divided into three subgroups, with the genetic diversity centers were located in Transcaucasia. Several candidate genes and SNP site associated with CNglcs content and growth traits were identified by genome-wide associated study (GWAS). A non-synonymous in LjMTR was responsible for the decreased expression of CNglcs synthesis genes and LjZCD was verified to positively regulate CNglcs synthesis gene CYP79D3. The LjZCB and an SNP in LjZCA promoter were confirmed to be involved in plant growth.CONCLUSION: This study provided a large number of genomic resources and described genetic relationship and population structure among different accessions. Moreover, we attempt to provide insights into the molecular studies and breeding of CNglcs and growth traits in L. corniculatus.PMID:37592232 | DOI:10.1186/s12915-023-01670-7

BMC Infect Dis. 2023 Aug 18;23(1):536. doi: 10.1186/s12879-023-08505-4.ABSTRACTBACKGROUND: The synergy between the human immunodeficiency virus (HIV) and Mycobacterium tuberculosis during co-infection of a host is well known. While this synergy is known to be driven by immunological deterioration, the metabolic mechanisms that contribute to the associated disease burden experienced during HIV/tuberculosis (TB) co-infection remain poorly understood. Furthermore, while anti-HIV treatments suppress viral replication, these therapeutics give rise to host metabolic disruption and adaptations beyond that induced by only infection or disease.METHODS: In this study, the serum metabolic profiles of healthy controls, untreated HIV-negative TB-positive patients, untreated HIV/TB co-infected patients, and HIV/TB co-infected patients on antiretroviral therapy (ART), were measured using two-dimensional gas chromatography time-of-flight mass spectrometry. Since no global metabolic profile for HIV/TB co-infection and the effect of ART has been published to date, this pilot study aimed to elucidate the general areas of metabolism affected during such conditions.RESULTS: HIV/TB co-infection induced significant changes to the host's lipid and protein metabolism, with additional microbial product translocation from the gut to the blood. The results suggest that HIV augments TB synergistically, at least in part, contributing to increased inflammation, oxidative stress, ART-induced mitochondrial damage, and its detrimental effects on gut health, which in turn, affects energy availability. ART reverses these trends to some extent in HIV/TB co-infected patients but not to that of healthy controls.CONCLUSION: This study generated several new hypotheses that could direct future metabolic studies, which could be combined with other research techniques or methodologies to further elucidate the underlying mechanisms of these changes.PMID:37592227 | DOI:10.1186/s12879-023-08505-4

Int J Obes (Lond). 2023 Aug 17. doi: 10.1038/s41366-023-01361-x. Online ahead of print.ABSTRACTINTRODUCTION: Intrauterine conditions and accelerating early growth are associated with childhood obesity. It is unknown, whether fetal programming affects the early growth and could alterations in the maternal-fetal metabolome be the mediating mechanism. Therefore, we aimed to assess the associations between maternal and cord blood metabolite profile and offspring early growth.METHODS: The RADIEL study recruited 724 women at high risk for gestational diabetes mellitus (GDM) BMI ≥ 30 kg/m2 and/or prior GDM) before or in early pregnancy. Blood samples were collected once in each trimester, and from cord. Metabolomics were analyzed by targeted nuclear magnetic resonance (NMR) technique. Following up on offsprings' first 2 years growth, we discovered 3 distinct growth profiles (ascending n = 80, intermediate n = 346, and descending n = 146) by using latent class mixed models (lcmm).RESULTS: From the cohort of mother-child dyads with available growth profile data (n = 572), we have metabolomic data from 232 mothers from 1st trimester, 271 from 2nd trimester, 277 from 3rd trimester and 345 from cord blood. We have data on 220 metabolites in each trimester and 70 from cord blood. In each trimester of pregnancy, the mothers of the ascending group showed higher levels of VLDL and LDL particles, and lower levels of HDL particles (p < 0.05). When adjusted for gestational age, birth weight, sex, delivery mode, and maternal smoking, there was an association with ascending profile and 2nd trimester total cholesterol in HDL2, 3rd trimester total cholesterol in HDL2 and in HDL, VLDL size and ratio of triglycerides to phosphoglycerides (TG/PG ratio) in cord blood (p ≤ 0.002).CONCLUSION: Ascending early growth was associated with lower maternal total cholesterol in HDL in 2nd and 3rd trimester, and higher VLDL size and more adverse TG/PG ratio in cord blood.CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, http://www.CLINICALTRIALS: com , NCT01698385.PMID:37592059 | DOI:10.1038/s41366-023-01361-x

Nat Commun. 2023 Aug 17;14(1):4634. doi: 10.1038/s41467-023-40222-z.ABSTRACTDeregulated oxidative metabolism is a hallmark of leukaemia. While tyrosine kinase inhibitors (TKIs) such as imatinib have increased survival of chronic myeloid leukaemia (CML) patients, they fail to eradicate disease-initiating leukemic stem cells (LSCs). Whether TKI-treated CML LSCs remain metabolically deregulated is unknown. Using clinically and physiologically relevant assays, we generate multi-omics datasets that offer unique insight into metabolic adaptation and nutrient fate in patient-derived CML LSCs. We demonstrate that LSCs have increased pyruvate anaplerosis, mediated by increased mitochondrial pyruvate carrier 1/2 (MPC1/2) levels and pyruvate carboxylase (PC) activity, in comparison to normal counterparts. While imatinib reverses BCR::ABL1-mediated LSC metabolic reprogramming, stable isotope-assisted metabolomics reveals that deregulated pyruvate anaplerosis is not affected by imatinib. Encouragingly, genetic ablation of pyruvate anaplerosis sensitises CML cells to imatinib. Finally, we demonstrate that MSDC-0160, a clinical orally-available MPC1/2 inhibitor, inhibits pyruvate anaplerosis and targets imatinib-resistant CML LSCs in robust pre-clinical CML models. Collectively these results highlight pyruvate anaplerosis as a persistent and therapeutically targetable vulnerability in imatinib-treated CML patient-derived samples.PMID:37591854 | DOI:10.1038/s41467-023-40222-z

Gut. 2023 Aug 17:gutjnl-2023-330196. doi: 10.1136/gutjnl-2023-330196. Online ahead of print.NO ABSTRACTPMID:37591699 | DOI:10.1136/gutjnl-2023-330196

Proc Natl Acad Sci U S A. 2023 Aug 22;120(34):e2302370120. doi: 10.1073/pnas.2302370120. Epub 2023 Aug 17.ABSTRACTLong-lived parasites evade host immunity through highly evolved molecular strategies. The murine intestinal helminth, Heligmosomoides polygyrus, down-modulates the host immune system through release of an immunosuppressive TGF-β mimic, TGM1, which is a divergent member of the CCP (Sushi) protein family. TGM1 comprises 5 domains, of which domains 1-3 (D1/2/3) bind mammalian TGF-β receptors, acting on T cells to induce Foxp3+ regulatory T cells; however, the roles of domains 4 and 5 (D4/5) remain unknown. We noted that truncated TGM1, lacking D4/5, showed reduced potency. Combination of D1/2/3 and D4/5 as separate proteins did not alter potency, suggesting that a physical linkage is required and that these domains do not deliver an independent signal. Coprecipitation from cells treated with biotinylated D4/5, followed by mass spectrometry, identified the cell surface protein CD44 as a coreceptor for TGM1. Both full-length and D4/5 bound strongly to a range of primary cells and cell lines, to a greater degree than D1/2/3 alone, although some cell lines did not respond to TGM1. Ectopic expression of CD44 in nonresponding cells conferred responsiveness, while genetic depletion of CD44 abolished enhancement by D4/5 and ablated the ability of full-length TGM1 to bind to cell surfaces. Moreover, CD44-deficient T cells showed attenuated induction of Foxp3 by full-length TGM1, to levels similar to those induced by D1/2/3. Hence, a parasite protein known to bind two host cytokine receptor subunits has evolved a third receptor specificity, which serves to raise the avidity and cell type-specific potency of TGF-β signaling in mammalian cells.PMID:37590410 | DOI:10.1073/pnas.2302370120

STAR Protoc. 2023 Aug 16;4(3):102400. doi: 10.1016/j.xpro.2023.102400. Online ahead of print.ABSTRACTPrimary metabolites are molecules of essential biochemical reactions that define the biological phenotype. All primary metabolites cannot be measured in a single analysis. In this protocol, we outline the multiplexed and quantitative measurement of 106 metabolites that cover the central part of primary metabolism. The protocol includes several sample preparation techniques and one liquid chromatography-mass spectrometry method. Then, we describe the steps of the bioinformatic data analysis to better understand the metabolic perturbations that may occur in a biological system. For complete details on the use and execution of this protocol, please refer to: Costanza et al.,1 Blomme et al.,2 Blomme et al.,3 Guillon et al.,4 Stuani et al.5.PMID:37590149 | DOI:10.1016/j.xpro.2023.102400

Nat Prod Res. 2023 Aug 17:1-6. doi: 10.1080/14786419.2023.2245114. Online ahead of print.ABSTRACTEndophytic fungi are known to be a rich source for anti-infective drugs. In this study, Aptenia cordifolia associated endophytic fungi were explored for the first time. Seven isolates were identified morphologically followed by screening of these fungi by plug diffusion assay which revealed their potential activity against Staphylococcus aureus (ATCC 9144), Bacillus cereus (ATCC 14579), Serratia marcescens (ATCC 14756), Fusarium oxysporum (ATCC 48112), and Aspergillus flavus (ATCC 22546). Additionally, the crude ethyl acetate extract of the most potent three isolates in plug diffusion assay showed that Aspergillus sp. ACEFR2 was the most potent as anti-infective in disc diffusion assay; Accordingly, Aspergillus sp. ACEFR2 was investigated using phylogenetic analysis and LC-HR-ESI-MS. The phylogenetic analysis placed the strain into the Aspergillus section Niger close related to few species including A. niger. Whereas the metabolomic profiling revealed the presence of diverse pool of metabolites. Furthermore, in silico molecular docking study was carried out to predict which compounds most likely responsible for the anti-infective activity.PMID:37590004 | DOI:10.1080/14786419.2023.2245114

Environ Sci Pollut Res Int. 2023 Aug 17. doi: 10.1007/s11356-023-29295-x. Online ahead of print.ABSTRACTAlgae plays a significant role for the primary production in the oligotrophic ecosystems such as the acid mine pit lakes. Graesiella sp. MA1 was a new acid-tolerant photosynthetic protist isolated from an acid mine pit lake. To understand the acid responses of Graesiella sp. MA1, its physiological changes and metabolomics were studied during long-term acid stress. Photosynthetic pigments, soluble proteins, and antioxidant systems of Graesiella sp. MA1 cells displayed two phases, the adaptation phase and the growth phase. During the adaptation phase, both photosynthetic pigments and soluble proteins were inhibited, while antioxidant activity of SOD, APX, and GSH were promoted to response to the organism's damage. Metabolomics results revealed lipids and organic acids were abundant components in Graesiella sp. MA1 cells. In response to acid stress, the levels of acid-dependent resistant amino acids, including glutamate, aspartate, arginine, proline, lysine, and histidine, accumulated continuously to maintain orderly intracellular metabolic processes. In addition, fatty acids were mainly unsaturated, which could improve the fluidity of the cell membranes under acid stress. Metabolomic and physiological changes showed that Graesiella sp. MA1 had tolerance during long-term acid stress and the potential to be used as a bioremediation strain for the acidic wastewater.PMID:37589846 | DOI:10.1007/s11356-023-29295-x

Am J Physiol Renal Physiol. 2023 Aug 17. doi: 10.1152/ajprenal.00113.2023. Online ahead of print.ABSTRACTObesity is a global epidemic and risk factor for the development of chronic kidney disease. Obesity induces systemic changes in metabolism, but how it affects kidney metabolism specifically is not known. Zebrafish have previously been shown to develop obesity related kidney pathology and dysfunction when fed hypercaloric diets. To understand the direct effects of obesity on kidney metabolic function, we treated zebrafish for 8 weeks with a control and an overfeeding diet. At the end of treatment, we assessed changes in kidney and fish weights and used electron microscopy to evaluate cell ultrastructure. We then performed an untargeted metabolomic analysis on the kidney tissue of fish using ultra-high performance liquid chromatography coupled high-resolution mass spectrometry, and used mummichog and gene set enrichment analysis to uncover differentially affected metabolic pathways. Kidney metabolomes differed significantly and consistently between the control and overfed diets. Among 9593 features, we identified 235 which were significantly different (p<0.05) between groups (125 upregulated in overfed diet, 110 downregulated). Pathway analysis demonstrated perturbations in glycolysis and fatty acid synthesis pathways, and analysis of specific metabolites points to perturbations in tryptophan metabolism. Our key findings show that diet induced obesity leads to metabolic changes in the kidney tissue itself and implicate specific metabolic pathways, including glycolysis and tryptophan metabolism in the pathogenesis of obesity related kidney disease, demonstrating the power of untargeted metabolomics to identify pathways of interest by directly interrogating kidney tissue.PMID:37589050 | DOI:10.1152/ajprenal.00113.2023

Front Microbiol. 2023 Jul 31;14:1223741. doi: 10.3389/fmicb.2023.1223741. eCollection 2023.ABSTRACTDairy propionibacteria are Gram positive Actinomycetota, routinely utilized as starters in Swiss type cheese making and highly appreciated for their probiotic properties and health promoting effects. In this work, within the frame of a circular economy approach, 47 Propionibacterium and Acidipropionibacterium spp. were isolated from goat cheese and milk, and ewe rumen liquor, and characterized in view of their possible utilization for the production of novel pro-bioactive food and feed on scotta, a lactose rich substrate and one of the main by-products of the dairy industry. The evaluation of the Minimum Inhibitory Concentration (MIC) of 13 among the most common antibiotics in clinical practice revealed a general susceptibility to ampicillin, gentamycin, streptomycin, vancomycin, chloramphenicol, and clindamycin while confirming a lower susceptibility to aminoglycosides and ciprofloxacin. Twenty-five isolates, that proved capable of lactose utilization as the sole carbon source, were then characterized for functional and biotechnological properties. Four of them, ascribed to Propionibacterium freudenreichii species, and harboring resistance to bile salts (growth at 0.7-1.56 mM of unconjugated bile salts), acid stress (>80% survival after 1 h at pH 2), osmostress (growth at up to 6.5% NaCl) and lyophilization (survival rate > 80%), were selected and inoculated in scotta. On this substrate the four isolates reached cell densities ranging from 8.11 ± 0.14 to 9.45 ± 0.06 Log CFU mL-1 and proved capable of producing different vitamin B9 vitamers after 72 h incubation at 30°C. In addition, the semi-quantitative analysis following the metabolomics profiling revealed a total production of cobalamin derivatives (vitamin B12) in the range 0.49-1.31 mg L-1, thus suggesting a full activity of the corresponding biosynthetic pathways, likely involving a complex interplay between folate cycle and methylation cycle required in vitamin B12 biosynthesis. These isolates appear interesting candidates for further ad-hoc investigation regarding the production of pro-bioactive scotta.PMID:37588883 | PMC:PMC10425813 | DOI:10.3389/fmicb.2023.1223741

Heliyon. 2023 Aug 5;9(8):e18891. doi: 10.1016/j.heliyon.2023.e18891. eCollection 2023 Aug.ABSTRACTThere are two major types of Wuyi Shuixian teas with distinct flavor properties in the market: regular Shuixian, and Laocong Shuixian that is produced from old tea plants with higher sale price. However, the chemical composition difference between these two types of Shuixian teas is still unclear. In this study, the widely targeted metabonomics and sensory evaluation were carried out to investigate the metabolite profiles and the flavor properties of Laocong and regular Shuixian tea samples. The results of organoleptic evaluation showed the Laocong Shuixian teas achieved dramatically higher total scores of sensory quality than that of regular Shuixian, and the sour palate of Laocong Shuixian tea was much lower than that of regular Shuxian. A total of 692 metabolites were identified by using metabolic determination, 43 of which were different metabolites in Laocong Shuixian teas discriminated from regular Shuixian. The contents of caffeic acid, kaemperfin, genistin, quercetin 3-glycosides and p-coumaric acid-O-glycoside were abundantly present in regular Shuixian tea. The analysis on different metabolites and taste attributes showed that phenolic acidic compounds were the major contributors to the sour taste of regular Shuixian. This study interpreted the chemicals underlying the different taste properties of Laocong and regular Shuixian teas.PMID:37588613 | PMC:PMC10425894 | DOI:10.1016/j.heliyon.2023.e18891

Front Med (Lausanne). 2023 Jul 31;10:1148542. doi: 10.3389/fmed.2023.1148542. eCollection 2023.ABSTRACTBACKGROUND: Breast cancer is a common malignant tumor. A large number of medical evidence shows that breast cancer screening can improve the early diagnosis rate and reduce the mortality rate of breast cancer. In the present study, a wide range of targeted metabolomics profiling was conducted to investigate the plasma signatures of breast cancer.METHODS: A total of 86 patients with benign breast abnormalities (L group) and 143 patients with breast cancer (E group) were recruited. We collected their plasma samples and clinical information. Metabolomic analysis, based on the coverage of a wide range of targeted metabolomics was conducted with ultraperformance liquid chromatography- triple quadrupole-linear ion trap mass spectrometer (UPLC-QTRAP-MS).RESULTS: We identified 716 metabolites through widely-targeted metabolomics. Serotonergic synapse was the main different metabolic pathway. The fold change of 14 metabolites was considered significantly different (fold change <0.67 or fold change >2; p < 0.05). By combining all the 14 metabolites, we achieved differentiation of L group vs. E group (AUC = 0.792, 95%Cl: 0.662-0.809).CONCLUSION: This study provided new insights into plasma biomarkers for differential diagnosis of benign abnormalities and breast cancer.PMID:37588002 | PMC:PMC10425771 | DOI:10.3389/fmed.2023.1148542

Eur J Mass Spectrom (Chichester). 2023 Aug 16:14690667231193555. doi: 10.1177/14690667231193555. Online ahead of print.ABSTRACTMass spectrometry (MS) has developed over the last decades into the most informative and versatile analytical technology in molecular and structural biology (). The platform enables discovery, identification, and characterisation of non-volatile biomolecules, such as proteins, peptides, DNA, RNA, nutrients, metabolites, and lipids at both speed and scale and can elucidate their interactions and effects. The versatility, robustness, and throughput have rendered MS a major research and development platform in molecular human health and biomedical science. More recently, MS has also been established as the central tool for 'Molecular Nutrition', enabling comprehensive and rapid identification and characterisation of macro- and micronutrients, bioactives, and other food compounds. 'Molecular Nutrition' thereby helps understand bioaccessibility, bioavailability, and bioefficacy of macro- and micronutrients and related health effects. Hence, MS provides a lens through which the fate of nutrients can be monitored along digestion via absorption to metabolism. This in turn provides the bioanalytical foundation for 'Personalised Nutrition' or 'Precision Nutrition' in which design and development of diets and nutritional products is tailored towards consumer and patient groups sharing similar genetic and environmental predisposition, health/disease conditions and lifestyles, and/or objectives of performance and wellbeing. The next level of integrated nutrition science is now being built as 'Systems Nutrition' where public and personal health data are correlated with life condition and lifestyle factors, to establish directional relationships between nutrition, lifestyle, environment, and health, eventually translating into science-based public and personal heath recommendations and actions. This account provides a condensed summary of the contributions of MS to a precise, quantitative, and comprehensive nutrition and health science and sketches an outlook on its future role in this fascinating and relevant field.PMID:37587732 | DOI:10.1177/14690667231193555