PubMed

Front Plant Sci. 2023 Sep 7;14:1281889. doi: 10.3389/fpls.2023.1281889. eCollection 2023.NO ABSTRACTPMID:37745987 | PMC:PMC10513781 | DOI:10.3389/fpls.2023.1281889

Front Genet. 2023 Sep 6;14:1219335. doi: 10.3389/fgene.2023.1219335. eCollection 2023.ABSTRACTIntroduction: Yanling Yinbiancha, a cultivar of Camellia sinensis (L.) O. Kuntze, is an evergreen woody perennial with characteristic albino leaves. A mutant variant with green leaves on branches has been recently identified. The molecular mechanisms underlying this color variation remain unknown. Methods: We aimed to utilize omics tools to decipher the molecular basis for this color variation, with the ultimate goal of enhancing existing germplasm and utilizing it in future breeding programs. Results and discussion: Albinotic leaves exhibited significant chloroplast degeneration and reduced carotenoid accumulation. Transcriptomic and metabolomic analysis of the two variants revealed 1,412 differentially expressed genes and 127 differentially accumulated metabolites (DAMs). Enrichment analysis for DEGs suggested significant enrichment of pathways involved in the biosynthesis of anthocyanins, porphyrin, chlorophyll, and carotenoids. To further narrow down the causal variation for albinotic leaves, we performed a conjoint analysis of metabolome and transcriptome and identified putative candidate genes responsible for albinism in C. sinensis leaves. 12, 7, and 28 DEGs were significantly associated with photosynthesis, porphyrin/chlorophyll metabolism, and flavonoid metabolism, respectively. Chlorophyllase 2, Chlorophyll a-Binding Protein 4A, Chlorophyll a-Binding Protein 24, Stay Green Regulator, Photosystem II Cytochrome b559 subunit beta along with transcription factors AP2, bZIP, MYB, and WRKY were identified as a potential regulator of albinism in Yanling Yinbiancha. Moreover, we identified Anthocyanidin reductase and Arabidopsis Response Regulator 1 as DEGs influencing flavonoid accumulation in albino leaves. Identification of genes related to albinism in C. sinensis may facilitate genetic modification or development of molecular markers, potentially enhancing cultivation efficiency and expanding the germplasm for utilization in breeding programs.PMID:37745858 | PMC:PMC10516542 | DOI:10.3389/fgene.2023.1219335

Front Endocrinol (Lausanne). 2023 Sep 8;14:1255889. doi: 10.3389/fendo.2023.1255889. eCollection 2023.ABSTRACTBACKGROUND: Senescence have emerged as potential factors of lung cancer risk based on findings from many studies. However, the underlying pathogenesis of lung cancer caused by senescence is not clear. In this study, we try to explain the potential pathogenesis between senescence and lung cancer through proteomics and metabonomics. And try to find new potential therapeutic targets in lung cancer patients through network mendelian randomization (MR).METHODS: The genome-wide association data of this study was mainly obtained from a meta-analysis and the Transdisciplinary Research in Cancer of the Lung Consortium (TRICL), respectively.And in this study, we mainly used genetic complementarity methods to explore the susceptibility of aging to lung cancer. Additionally, a mediation analysis was performed to explore the potential mediating role of proteomics and metabonomics, using a network MR design.RESULTS: GNOVA analysis revealed a shared genetic structure between HannumAge and lung cancer with a significant genetic correlation estimated at 0.141 and 0.135, respectively. MR analysis showed a relationship between HannumAge and lung cancer, regardless of smoking status. Furthermore, genetically predicted HannumAge was consistently associated with the proteins C-type lectin domain family 4 member D (CLEC4D) and Retinoic acid receptor responder protein 1 (RARR-1), indicating their potential role as mediators in the causal pathway.CONCLUSION: HannumAge acceleration may increase the risk of lung cancer, some of which may be mediated by CLEC4D and RARR-1, suggestion that CLEC4D and RARR-1 may serve as potential drug targets for the treatment of lung cancer.PMID:37745724 | PMC:PMC10514473 | DOI:10.3389/fendo.2023.1255889

Front Endocrinol (Lausanne). 2023 Sep 6;14:1211015. doi: 10.3389/fendo.2023.1211015. eCollection 2023.ABSTRACTAIMS/HYPOTHESIS: Appearance of multiple islet cell autoantibodies in early life is indicative of future progression to overt type 1 diabetes, however, at varying rates. Here, we aimed to study whether distinct metabolic patterns could be identified in rapid progressors (RP, disease manifestation within 18 months after the initial seroconversion to autoantibody positivity) vs. slow progressors (SP, disease manifestation at 60 months or later from the appearance of the first autoantibody).METHODS: Longitudinal samples were collected from RP (n=25) and SP (n=41) groups at the ages of 3, 6, 12, 18, 24, or ≥ 36 months. We performed a comprehensive metabolomics study, analyzing both polar metabolites and lipids. The sample series included a total of 239 samples for lipidomics and 213 for polar metabolites.RESULTS: We observed that metabolites mediated by gut microbiome, such as those involved in tryptophan metabolism, were the main discriminators between RP and SP. The study identified specific circulating molecules and pathways, including amino acid (threonine), sugar derivatives (hexose), and quinic acid that may define rapid vs. slow progression to type 1 diabetes. However, the circulating lipidome did not appear to play a major role in differentiating between RP and SP.CONCLUSION/INTERPRETATION: Our study suggests that a distinct metabolic profile is linked with the type 1 diabetes progression. The identification of specific metabolites and pathways that differentiate RP from SP may have implications for early intervention strategies to delay the development of type 1 diabetes.PMID:37745723 | PMC:PMC10516565 | DOI:10.3389/fendo.2023.1211015

bioRxiv. 2023 Sep 15:2023.09.12.557189. doi: 10.1101/2023.09.12.557189. Preprint.ABSTRACTMass spectrometry is a powerful and widely used tool for generating proteomics, lipidomics, and metabolomics profiles, which is pivotal for elucidating biological processes and identifying biomarkers. However, missing values in spectrometry-based omics data may pose a critical challenge for the comprehensive identification of biomarkers and elucidation of the biological processes underlying human complex disorders. To alleviate this issue, various imputation methods for mass spectrometry-based omics data have been developed. However, a comprehensive and systematic comparison of these imputation methods is still lacking, and researchers are frequently confronted with a multitude of options without a clear rationale for method selection. To address this pressing need, we developed omicsMIC (mass spectrometrybased omics with Missing values Imputation methods Comparison platform), an interactive platform that provides researchers with a versatile framework to simulate and evaluate the performance of 28 diverse imputation methods. omicsMIC offers a nuanced perspective, acknowledging the inherent heterogeneity in biological data and the unique attributes of each dataset. Our platform empowers researchers to make data-driven decisions in imputation method selection based on real-time visualizations of the outcomes associated with different imputation strategies. The comprehensive benchmarking and versatility of omicsMIC make it a valuable tool for the scientific community engaged in mass spectrometry-based omics research. OmicsMIC is freely available at https://github.com/WQLin8/omicsMIC .PMID:37745599 | PMC:PMC10515867 | DOI:10.1101/2023.09.12.557189

bioRxiv. 2023 Sep 16:2023.09.15.558013. doi: 10.1101/2023.09.15.558013. Preprint.ABSTRACTThe heart contracts incessantly and requires a constant supply of energy, utilizing numerous metabolic substrates such as fatty acids, carbohydrates, lipids, and amino acids to supply its high energy demands. Therefore, a comprehensive analysis of various metabolites is urgently needed for understanding cardiac metabolism; however, complete metabolome analyses remain challenging due to the broad range of metabolite polarities which makes extraction and detection difficult. Herein, we implemented parallel metabolite extractions and high-resolution mass spectrometry (MS)-based methods to obtain a comprehensive analysis of the human heart metabolome. To capture the diverse range of metabolite polarities, we first performed six parallel liquid-liquid extractions (three monophasic, two biphasic, and one triphasic extractions) of healthy human donor heart tissue. Next, we utilized two complementary MS platforms for metabolite detection - direct-infusion ultrahigh-resolution Fourier-transform ion cyclotron resonance (DI-FTICR) and high-resolution liquid chromatography quadrupole time-of-flight tandem MS (LC-Q-TOF MS/MS). Using DI-FTICR MS, 9,521 metabolic features were detected where 7,699 were assigned a chemical formula and 1,756 were assigned an annotated by accurate mass assignment. Using LC-Q-TOF MS/MS, 21,428 metabolic features were detected where 626 metabolites were identified based on fragmentation matching against publicly available libraries. Collectively, 2276 heart metabolites were identified in this study which span a wide range of polarities including polar (benzenoids, alkaloids and derivatives and nucleosides) as well as non-polar (phosphatidylcholines, acylcarnitines, and fatty acids) compounds. The results of this study will provide critical knowledge regarding the selection of appropriate extraction and MS detection methods for the analysis of the diverse classes of human heart metabolites.PMID:37745334 | PMC:PMC10516009 | DOI:10.1101/2023.09.15.558013

Front Vet Sci. 2023 Sep 8;10:1255122. doi: 10.3389/fvets.2023.1255122. eCollection 2023.ABSTRACTPre-weaning is the most important period for the growth and development of calves. Intestinal morphology, microbial community and immunity are initially constructed at this stage, and even have a lifelong impact on calves. Early feeding patterns have a significant impact on gastrointestinal development and microbial communities. This study mainly analyzed the effects of three feeding methods on the gastrointestinal development of calves, and provided a theoretical basis for further improving the feeding mode of calves. it is very important to develop a suitable feeding mode. In this study, we selected nine newborn healthy Holstein bull calves were randomly selected and divided into three groups (n = 3), which were fed with starter + hay + milk (SH group), starter + milk (SF group), total mixed ration + milk (TMR group). After 80 days of feeding Feeding to 80 days of age after, the ileum contents and blood samples were collected, and the differences were compared and analyzed by metagenomic analysis and serum metabolomics analysis. Results show that compared with the other two groups, the intestinal epithelium of the SH group was more complete and the goblet cells developed better. The feeding method of SH group was more conducive to the development of calves, with higher daily gain and no pathological inflammatory reaction. The intestinal microbial community was more conducive to digestion and absorption, and the immunity was stronger. These findings are helpful for us to explore better calf feeding patterns. In the next step, we will set up more biological replicates to study the deep-seated reasons for the differences in the development of pre-weaning calves. At the same time, the new discoveries of neuro microbiology broaden our horizons and are the focus of our future attention.PMID:37745216 | PMC:PMC10514501 | DOI:10.3389/fvets.2023.1255122

Front Cardiovasc Med. 2023 Sep 8;10:1197451. doi: 10.3389/fcvm.2023.1197451. eCollection 2023.ABSTRACTBACKGROUND: Results from randomized controlled trials (RCTs) and meta-analyses comparing invasive and conservative strategies in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) are highly debatable. We systematically evaluate the efficacy of invasive and conservative strategies in NSTE-ACS based on time-varied outcomes.METHODS: The RCTs for the invasive versus conservative strategies were identified by searching PubMed, Cochrane Central Register of Controlled Trials, Embase, and ClinicalTrials.gov. Trial data for studies with a minimum follow-up time of 30 days were included. We categorized the follow-up time into six varied periods, namely, ≤6 months, 1 year, 2 years, 3 years, 5 years, and ≥10 years. The time-varied outcomes were major adverse cardiovascular event (MACE), death, myocardial infarction (MI), rehospitalization, cardiovascular death, bleeding, in-hospital death, and in-hospital bleeding. Risk ratios (RRs) and 95% confidence intervals (Cis) were calculated. The random effects model was used.RESULTS: This meta-analysis included 30 articles of 17 RCTs involving 12,331 participants. We found that the invasive strategy did not provide appreciable benefits for NSTE-ACS in terms of MACE, death, and cardiovascular death at all time points compared with the conservative strategy. Although the risk of MI was reduced within 6 months (RR 0.80, 95% CI 0.68-0.94) for the invasive strategy, no significant differences were observed in other periods. The invasive strategy reduced the rehospitalization rate within 6 months (RR 0.69, 95% CI 0.52-0.90), 1 year (RR 0.73, 95% CI 0.63-0.86), and 2 years (RR 0.77, 95% CI 0.60-1.00). Of note, an increased risk of bleeding (RR 1.80, 95% CI 1.28-2.54) and in-hospital bleeding (RR 2.17, 95% CI 1.52-3.10) was observed for the invasive strategy within 6 months. In subgroups stratified by high-risk features, the invasive strategy decreased MACE for patients aged ≥65 years within 6 months (RR 0.68, 95% CI 0.58-0.78) and 1 year (RR 0.75, 95% CI 0.62-0.91) and showed benefits for men within 6 months (RR 0.71, 95% CI 0.55-0.92). In other subgroups stratified according to diabetes, ST-segment deviation, and troponin levels, no significant differences were observed between the two strategies.CONCLUSIONS: An invasive strategy is superior to a conservative strategy in reducing early events for MI and rehospitalizations, but the invasive strategy did not improve the prognosis in long-term outcomes for patients with NSTE-ACS.SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021289579, identifier PROSPERO 2021 CRD42021289579.PMID:37745128 | PMC:PMC10516546 | DOI:10.3389/fcvm.2023.1197451

Front Cardiovasc Med. 2023 Sep 7;10:1251122. doi: 10.3389/fcvm.2023.1251122. eCollection 2023.ABSTRACTBACKGROUND: Prolonged fasting, characterized by restricting caloric intake for 24 h or more, has garnered attention as a nutritional approach to improve lifespan and support healthy aging. Previous research from our group showed that a single bout of 36-h water-only fasting in humans resulted in a distinct metabolomic signature in plasma and increased levels of bioactive metabolites, which improved macrophage function and lifespan in C. elegans.OBJECTIVE: This secondary outcome analysis aimed to investigate changes in the plasma lipidome associated with prolonged fasting and explore any potential links with markers of cardiometabolic health and aging.METHOD: We conducted a controlled pilot study with 20 male and female participants (mean age, 27.5 ± 4.4 years; mean BMI, 24.3 ± 3.1 kg/m2) in four metabolic states: (1) overnight fasted (baseline), (2) 2-h postprandial fed state (fed), (3) 36-h fasted state (fasted), and (4) 2-h postprandial refed state 12 h after the 36-h fast (refed). Plasma lipidomic profiles were analyzed using liquid chromatography and electrospray ionization mass spectrometry.RESULTS: Several lipid classes, including lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), phosphatidylethanolamine, and triacylglycerol were significantly reduced in the 36-h fasted state, while free fatty acids, ceramides, and sphingomyelin were significantly increased compared to overnight fast and fed states (P < 0.05). After correction for multiple testing, 245 out of 832 lipid species were significantly altered in the fasted state compared to baseline (P < 0.05). Random forest models revealed that several lipid species, such as LPE(18:1), LPC(18:2), and FFA(20:1) were important features in discriminating the fasted state from both the overnight fasted and postprandial state.CONCLUSION: Our findings indicate that prolonged fasting vastly remodels the plasma lipidome and markedly alters the concentrations of several lipid species, which may be sensitive biomarkers of prolonged fasting. These changes in lipid metabolism during prolonged fasting have important implications for the management of cardiometabolic health and healthy aging, and warrant further exploration and validation in larger cohorts and different population groups.PMID:37745091 | PMC:PMC10513913 | DOI:10.3389/fcvm.2023.1251122

Food Chem X. 2023 Sep 9;19:100873. doi: 10.1016/j.fochx.2023.100873. eCollection 2023 Oct 30.ABSTRACTTo obtain flavor-enriched Tibetan pork products, the impact of oxidation degree on the flavor of Tibetan pork with different cooking methods (microwaving, frying, boiling, and air frying) was evaluated using an E-nose, an E-tongue, GC-MS, and LC-MS. The level of oxidation was lower in M and F and higher in B and AF groups. Hexanal, pentanal, benzaldehyde, 1-octen-3-ol, and 3-hydroxy-2-butanone were identified as significant contributors to cooked samples. The volatile abundance of microwaved, fried, boiled, and air-fried pork was 1.61, 1.22, 1.47, and 1.69 times higher than raw, respectively. Leucine and threonine were detected to be the highest in the AF group, which were 1.30 and 3.60 times greater than RAW, respectively. In summary, oxidation of lipids and proteins caused by cooking treatments was the main source of flavor in cooked Tibetan pork. Air-frying treatment could greatly promote the production of flavor compounds and give unique flavor to Tibetan pork.PMID:37745033 | PMC:PMC10511784 | DOI:10.1016/j.fochx.2023.100873

iScience. 2023 Aug 29;26(9):107594. doi: 10.1016/j.isci.2023.107594. eCollection 2023 Sep 15.ABSTRACTLeishmaniasis is a tropical disease prevalent in 90 countries. Presently, there is no approved vaccine for human use. We developed a live attenuated L. mexicana Cen-/-(LmexCen-/-) strain as a vaccine candidate that showed excellent efficacy, characterized by reduced Th2 and enhanced Th1 responses in C57BL/6 and BALB/c mice, respectively, compared to wild-type L. mexicana (LmexWT) infection. Toward understanding the immune mechanisms of protection, we applied untargeted mass spectrometric analysis to LmexCen-/- and LmexWT infections. Data showed enrichment of the pentose phosphate pathway (PPP) in ears immunized with LmexCen-/-versus naive and LmexWT infection. PPP promotes M1 polarization in macrophages, suggesting a switch to a pro-inflammatory phenotype following LmexCen-/- inoculation. Accordingly, PPP inhibition in macrophages infected with LmexCen-/- reduced the production of nitric oxide and interleukin (IL)-1β, hallmarks of classical activation. Overall, our study revealed the immune regulatory mechanisms that may be critical for the induction of protective immunity.PMID:37744404 | PMC:PMC10517399 | DOI:10.1016/j.isci.2023.107594

iScience. 2023 Aug 29;26(9):107593. doi: 10.1016/j.isci.2023.107593. eCollection 2023 Sep 15.ABSTRACTLeishmaniasis is a parasitic disease that is prevalent in 90 countries, and yet no licensed human vaccine exists against it. Toward control of leishmaniasis, we have developed Leishmania major centrin gene deletion mutant strains (LmCen-/-) as a live attenuated vaccine, which induces a strong IFN-γ-mediated protection to the host. However, the immune mechanisms of such protection remain to be understood. Metabolomic reprogramming of the host cells following Leishmania infection has been shown to play a critical role in pathogenicity and shaping the immune response following infection. Here, we applied untargeted mass spectrometric analysis to study the metabolic changes induced by infection with LmCen-/- and compared those with virulent L. major parasite infection to identify the immune mechanism of protection. Our data show that immunization with LmCen-/- parasites, in contrast to virulent L. major infection promotes a pro-inflammatory response by utilizing tryptophan to produce melatonin and downregulate anti-inflammatory kynurenine-AhR and FICZ-AhR signaling.PMID:37744403 | PMC:PMC10517402 | DOI:10.1016/j.isci.2023.107593

Front Immunol. 2023 Sep 6;14:1267194. doi: 10.3389/fimmu.2023.1267194. eCollection 2023.ABSTRACTChronic rhinosinusitis with nasal polyps (CRSwNP) is a complex and heterogeneous disease, typically diagnosed through endoscopy and computed tomography and treated with glucocorticoid or surgery. There is an urgent need to develop molecular-level diagnostic or prognostic tools to better understand the pathophysiology of CRSwNP. Proteomics and metabolomics, emerging fields, offer significant potential in elucidating the mechanisms underlying CRSwNP. Mass spectrometry, a powerful and sensitive tool for trace substance detection, is broadly applied for proteomics and metabolomics analysis in CRSwNP research. While previous literature has summarized the advancement of mass spectrometry-based CRSwNP proteomics from 2004 to 2018, recent years have seen new advances in this field, particularly about non-invasive samples and exosomes. Furthermore, mass spectrometry-based CRSwNP metabolomics research has opened new avenues for inquiry. Therefore, we present a comprehensive review of mass spectrometry-based proteomics and metabolomics studies on CRSwNP conducted between 2019 and 2022. Specifically, we highlight protein and metabolic biomarkers that have been utilized as diagnostic or prognostic markers for CRSwNP. Lastly, we conclude with potential directions for future mass spectrometry-based omics studies of CRSwNP.PMID:37744372 | PMC:PMC10511644 | DOI:10.3389/fimmu.2023.1267194

Oncol Res. 2023 Sep 15;31(6):877-885. doi: 10.32604/or.2023.029494. eCollection 2023.ABSTRACTSpatial omics technology integrates the concept of space into omics research and retains the spatial information of tissues or organs while obtaining molecular information. It is characterized by the ability to visualize changes in molecular information and yields intuitive and vivid visual results. Spatial omics technologies include spatial transcriptomics, spatial proteomics, spatial metabolomics, and other technologies, the most widely used of which are spatial transcriptomics and spatial proteomics. The tumor microenvironment refers to the surrounding microenvironment in which tumor cells exist, including the surrounding blood vessels, immune cells, fibroblasts, bone marrow-derived inflammatory cells, various signaling molecules, and extracellular matrix. A key issue in modern tumor biology is the application of spatial omics to the study of the tumor microenvironment, which can reveal problems that conventional research techniques cannot, potentially leading to the development of novel therapeutic agents for cancer. This paper summarizes the progress of research on spatial transcriptomics and spatial proteomics technologies for characterizing the tumor immune microenvironment.PMID:37744276 | PMC:PMC10513957 | DOI:10.32604/or.2023.029494

Oncol Res. 2023 Sep 15;31(6):833-844. doi: 10.32604/or.2023.030241. eCollection 2023.ABSTRACTDihydroorotate dehydrogenase (DHODH) is a central enzyme of the de novo pyrimidine biosynthesis pathway and is a promising drug target for the treatment of cancer and autoimmune diseases. This study presents the identification of a potent DHODH inhibitor by proteomic profiling. Cell-based screening revealed that NPD723, which is reduced to H-006 in cells, strongly induces myeloid differentiation and inhibits cell growth in HL-60 cells. H-006 also suppressed the growth of various cancer cells. Proteomic profiling of NPD723-treated cells in ChemProteoBase showed that NPD723 was clustered with DHODH inhibitors. H-006 potently inhibited human DHODH activity in vitro, whereas NPD723 was approximately 400 times less active than H-006. H-006-induced cell death was rescued by the addition of the DHODH product orotic acid. Moreover, metabolome analysis revealed that H-006 treatment promotes marked accumulation of the DHODH substrate dihydroorotic acid. These results suggest that NPD723 is reduced in cells to its active metabolite H-006, which then targets DHODH and suppresses cancer cell growth. Thus, H-006-related drugs represent a potentially powerful treatment for cancer and other diseases.PMID:37744270 | PMC:PMC10513951 | DOI:10.32604/or.2023.030241

PeerJ. 2023 Sep 20;11:e16077. doi: 10.7717/peerj.16077. eCollection 2023.ABSTRACTBACKGROUND: Madin-Darby canine kidney (MDCK) cells are a cellular matrix in the production of influenza vaccines. The proliferation rate of MDCK cells is one of the critical factors that determine the vaccine production cycle. It is yet to be determined if there is a correlation between cell proliferation and alterations in metabolic levels. This study aimed to explore the metabolic differences between MDCK cells with varying proliferative capabilities through the use of both untargeted and targeted metabolomics.METHODS: To investigate the metabolic discrepancies between adherent cell groups (MDCK-M60 and MDCK-CL23) and suspension cell groups (MDCK-XF04 and MDCK-XF06), untargeted and targeted metabolomics were used. Utilizing RT-qPCR analysis, the mRNA expressions of key metabolites enzymes were identified.RESULTS: An untargeted metabolomics study demonstrated the presence of 81 metabolites between MDCK-M60 and MDCK-CL23 cells, which were mainly affected by six pathways. An analysis of MDCK-XF04 and MDCK-XF06 cells revealed a total of 113 potential metabolites, the majority of which were impacted by ten pathways. Targeted metabolomics revealed a decrease in the levels of choline, tryptophan, and tyrosine in MDCK-CL23 cells, which was in accordance with the results of untargeted metabolomics. Additionally, MDCK-XF06 cells experienced a decrease in 5'-methylthioadenosine and tryptophan, while S-adenosylhomocysteine, kynurenine, 11Z-eicosenoic acid, 3-phosphoglycerate, glucose 6-phosphate, and phosphoenolpyruvic acid concentrations were increased. The mRNA levels of MAT1A, MAT2B, IDO1, and IDO2 in the two cell groups were all increased, suggesting that S-adenosylmethionine and tryptophan may have a significant role in cell metabolism.CONCLUSIONS: This research examines the effect of metabolite fluctuations on cell proliferation, thus offering a potential way to improve the rate of MDCK cell growth.PMID:37744241 | PMC:PMC10517658 | DOI:10.7717/peerj.16077

Front Fungal Biol. 2021 May 25;2:681631. doi: 10.3389/ffunb.2021.681631. eCollection 2021.ABSTRACTTannic acid, a hydrolysable gallotannin present in plant tissues, consists of a central glucose molecule esterified with gallic acid molecules. Some microorganisms, including several Aspergillus species, can metabolize tannic acid by releasing gallic acid residues from tannic acid by secreting tannic acid specific esterases into the medium. The expression of these so-called tannases is induced by tannic acid or gallic acid. In this study, we identified a conserved transcriptional activator-repressor module involved in the regulation of predicted tannases and other genes involved in gallic acid metabolism. The transcriptional activator-repressor module regulating tannic acid utilization resembles the transcriptional activator-repressor modules regulating galacturonic acid and quinic acid utilization. Like these modules, the Zn(II)2Cys6 transcriptional activator (TanR) and the putative repressor (TanX) are located adjacent to each other. Deletion of the transcriptional activator (ΔtanR) results in inability to grow on gallic acid and severely reduces growth on tannic acid. Deletion of the putative repressor gene (ΔtanX) results in the constitutive expression of tannases as well as other genes with mostly unknown function. Known microbial catabolic pathways for gallic acid utilization involve so-called ring cleavage enzymes, and two of these ring cleavage enzymes show increased expression in the ΔtanX mutant. However, deletion of these two genes, and even deletion of all 17 genes encoding potential ring cleavage enzymes, did not result in a gallic acid non-utilizing phenotype. Therefore, in A. niger gallic acid utilization involves a hitherto unknown pathway. Transcriptome analysis of the ΔtanX mutant identified several genes and gene clusters that were significantly induced compared to the parental strain. The involvement of a selection of these genes and gene clusters in gallic acid utilization was examined by constructing gene deletion mutants and testing their ability to grow on gallic acid. Only the deletion of a gene encoding an FAD-dependent monooxygenase (NRRL3_04659) resulted in a strain that was unable to grow on gallic acid. Metabolomic studies showed accumulation of gallic acid in the ΔNRRL3_04659 mutant suggesting that this predicted monooxygenase is involved in the first step of gallic acid metabolism and is likely responsible for oxidation of the aromatic ring.PMID:37744122 | PMC:PMC10512348 | DOI:10.3389/ffunb.2021.681631

Front Nutr. 2023 Sep 7;10:1268633. doi: 10.3389/fnut.2023.1268633. eCollection 2023.ABSTRACTSea buckthorn has a high nutritional value, but its sour taste and foul odor make it unpalatable for consumers. In this study, we analyzed the metabolite changes occurring during the yeast-assisted fermentation of sea buckthorn juice using the HeadSpace Solid-Phase Microextraction Gas Chromatography-Mass Spectrometry (HS-SPME-GC-MS) and Ultra-High Performance Liquid Chromatography-Mass Spectrometry (UHPLC-MS) techniques. A total of 86 volatile aroma compounds were identified during the fermentation process. The content of total volatiles in sea buckthorn juice increased by 3469.16 μg/L after 18 h of fermentation, with 22 compounds showing elevated levels. Notably, the total content of esters with fruity, floral, and sweet aromas increased by 1957.09 μg/L. We identified 379 non-volatile metabolites and observed significant increases in the relative abundance of key active ingredients during fermentation: glycerophosphorylcholine (increased by 1.54), glutathione (increased by 1.49), L-glutamic acid (increased by 2.46), and vanillin (increased by 0.19). KEGG pathway analysis revealed that amino acid metabolism and lipid metabolism were the primary metabolic pathways involved during fermentation by Saccharomyces cerevisiae. Fermentation has been shown to improve the flavor of sea buckthorn juice and increase the relative content of bioactive compounds. This study provides novel insights into the metabolic dynamics of sea buckthorn juice following yeast fermentation through metabolomics analysis. These findings could serve as a theoretical foundation for further studies on the factors influencing differences in yeast fermentation.PMID:37743927 | PMC:PMC10512423 | DOI:10.3389/fnut.2023.1268633

Analyst. 2023 Sep 25. doi: 10.1039/d3an01237a. Online ahead of print.ABSTRACTRecently, amino acids other than glycine and taurine were found to be conjugated with bile acids by the gut microbiome in mouse and human. As potential diagnostic markers for inflammatory bowel disease and farnesoid X receptor agonists, their physiological effects and mechanisms, however, remain to be elucidated. A tool for the rapid and comprehensive annotation of such new metabolites is required. Thus, we developed a semi-empirical MS/MS library for bile acids conjugated with 18 common amino acids, including alanine, arginine, asparagine, aspartate, glutamine, glutamate, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine. To investigate their fragmentation rules, these amino acids were chemically conjugated with lithocholic acid, deoxycholic acid, and cholic acid, and their accurate-mass MS/MS spectra were acquired. The common fragmentation patterns from the amino acid moieties were combined with 10 general bile acid skeletons to generate a semi-empirical MS/MS library of 180 structures. Software named BAFinder 2.0 was developed to combine the semi-empirical library in negative mode and the characteristic fragments in positive mode for automatic unknown identification. As a proof of concept, this workflow was applied to the LC-MS/MS analysis of the feces of human, beagle dogs, and rats. In total, 171 common amino acid-conjugated bile acids were annotated and 105 of them were confirmed with the retention times of synthesized compounds. To explore other potential bile acid conjugates, user-defined small molecules were in-silico conjugated with bile acids and searched in the fecal dataset. Four novel bile acid conjugates were discovered, including D-Ala-D-Ala, Lys(iso)-Gly, L-2-aminobutyric acid, and ornithine.PMID:37743718 | DOI:10.1039/d3an01237a

Adv Mater. 2023 Sep 24:e2307263. doi: 10.1002/adma.202307263. Online ahead of print.ABSTRACTUnsatisfied tumor accumulation of chemotherapeutic drugs and a complicated immunosuppressive microenvironment diminish the immune response rate and the therapeutic effect. Surface modification of these drugs with target ligands can promote their cellular internalization, but the modified drugs may be subjected to unexpected immune recognition and clearance. Herein, a phenylboronic acid (PBA) group-shieldable dendritic nanomedicine that integrates an immunogenic cell death (ICD)-inducing agent (epirubicin, Epi) and an indoleamine 2,3-dioxgenase 1 (IDO1) inhibitor (NLG919) is reported for tumor chemo-immunotherapy. This NLG919-loaded Epi-conjugated PEGylated dendrimers bridged with boronate bonds (NLG919@Epi-DBP) maintains a stable nanostructure during circulation. Under a moderate acidic condition, the PBA group exposes to the sialic acid residue on the tumor cell membrane to enhance the internalization and penetration of NLG919@Epi-DBP. At pH 5.0, NLG919@Epi-DBP rapidly disassembles to release the incorporated Epi and NLG919. Epi triggers robust ICD of tumor cells that evokes strong immune response. In addition, inhibition of the IDO1 activity downregulates the metabolism of L-tryptophan to kynurenine, leading to a reduction in the recruitment of immunosuppressive cells and modulation of the tumor immune microenvironment. Collectively, this promising strategy has been demonstrated to evoke robust immune response as well as remodel the immunosuppressive microenvironment for an enhanced chemo-immunotherapeutic effect. This article is protected by copyright. All rights reserved.PMID:37743633 | DOI:10.1002/adma.202307263