PubMed

J Chromatogr B Analyt Technol Biomed Life Sci. 2024 Jun 22;1244:124214. doi: 10.1016/j.jchromb.2024.124214. Online ahead of print.ABSTRACTC. madagascariensis, an unexplored species of Burseraceae is used by local population for the management of inflammation and throat pain. The disease alleviation by this plant could be due to the presence of rich repository of active compounds with various pharmacological importances. In this study, therefore, the profiling of metabolites and isolation of active compounds of C. madagascariensis was performed. Furthermore, the ethanol, ethyl acetate extracts and a selected active compound was subjected for in vitro and in vivo anti-inflammatory activities. Metabolomic analysis identified and quantified 116 metabolites from leaves, young stem and gum-resins of C. madagascariensis (Burseraceae) followed by multivariate PCA analysis. NMR, GC-MS and HPLC were used to analyze primary and secondary metabolites. Subsequently, five main isolated compounds were identified as trimethoxy tetrahydrobenzo dioxolo isochromene (TTDI), butyl phenol, butyl propionate phenol, germacrone and β-elemenone. Amongst them, TTDI was found to be a novel compound. Hence, a process was developed to obtain the enriched fraction of TTDI in ethanol and ethyl acetate extracts of leaves. Furthermore, TTDI and extracts were subjected for their in vitro anti-inflammatory activity in LPS sensitized murine splenocytes. The results showed that TTDI and both extracts significantly suppressed the levels of pro-inflammatorycytokines (TNF-α, IFN-γ). Interestingly, the suppression of pro-inflammatory cytokines was evenmore significant by the similar concentration of TTDI when compared with colchicine. However, the level of anti-inflammatory cytokine (IL-10) was found to be unchanged. Additionally, in vivo anti-inflammatory study revealed a significant reduction in carrageenan induced paw edema by TTDI and both the extracts. In the docking study, TTDI was more active than colchicine with strong binding affinity to COX-2, PLA2, and 5β reductase. Our results highlighted that the presence of metabolites with medicinal and nutraceutical importance in C. madagascariensis, could provide opportunities for the development of a new plant-based therapeutics for inflammation.PMID:39032480 | DOI:10.1016/j.jchromb.2024.124214

Eur J Obstet Gynecol Reprod Biol. 2024 Jul 19;300:224-229. doi: 10.1016/j.ejogrb.2024.07.026. Online ahead of print.ABSTRACTBACKGROUND: Recent studies have suggested that pregnancy accelerates biologic aging, yet little is known about how biomarkers of aging are affected by events during the peripartum period. Given that immune shifts are known to occur following surgery, we explored the relation between mode of delivery and postpartum maternal leukocyte telomere length (LTL), a marker of biologic aging.STUDY DESIGN: Postpartum maternal blood samples were obtained from a prospective cohort of term, singleton livebirths without hypertensive disorders or peripartum infections between 2012 and 2018. The primary outcome was postpartum LTLs from one blood sample drawn between postpartum week 1 and up to 6 months postpartum, measured from thawed frozen peripheral blood mononuclear cells using quantitative PCR in basepairs (bp). Multivariable linear regression models compared LTLs between vaginal versus cesarean births, adjusting for age, body mass index, and nulliparity as potential confounders. Analyses were conducted in two mutually exclusive groups: those with LTL measured postpartum week 1 and those measured up to 6 months postpartum. Secondarily, we compared multiomics by mode of delivery using machine-learning methods to evaluate whether other biologic changes occurred following cesarean. These included transcriptomics, metabolomics, microbiomics, immunomics, and proteomics (serum and plasma).RESULTS: Of 67 included people, 50 (74.6 %) had vaginal and 17 (25.4 %) had cesarean births. LTLs were significantly shorter after cesarean in postpartum week 1 (5755.2 bp cesarean versus 6267.8 bp vaginal, p = 0.01) as well as in the later draws (5586.6 versus 5945.6 bp, p = 0.04). After adjusting for confounders, these differences persisted in both week 1 (adjusted beta -496.1, 95 % confidence interval [CI] -891.1, -101.1, p = 0.01) and beyond (adjusted beta -396.8; 95 % CI -727.2, -66.4. p = 0.02). Among the 15 participants who also had complete postpartum multiomics data available, there were predictive signatures of vaginal versus cesarean births in transcriptomics (cell-free [cf]RNA), metabolomics, microbiomics, and proteomics that did not persist after false discovery correction.CONCLUSION: Maternal LTLs in postpartum week 1 were nearly 500 bp shorter following cesarean. This difference persisted several weeks postpartum, even though other markers of inflammation had normalized. Mode of delivery should be considered in any analyses of postpartum LTLs and further investigation into this phenomenon is warranted.PMID:39032311 | DOI:10.1016/j.ejogrb.2024.07.026

Food Chem. 2024 Jul 15;460(Pt 1):140440. doi: 10.1016/j.foodchem.2024.140440. Online ahead of print.ABSTRACTThere has been limited research on external browning (EB) of walnut. This work discovered 1888 metabolites and 34 anthocyanins in walnut pellicles (WPs) after three drying methods using widely-targeted and anthocyanin-targeted metabolomics. Based on OPLS-DA and correlation analysis, 64 temperature-responsive metabolites (TRMs; 13 anthocyanins and 51 flavonoids) were identified as critical components in relation to EB. Notably, 14 flavonoids exhibited a strong positive correlation (r > 0.9) with the browning index (BI), with upregulation of >60% after browning. Most of the identified anthocyanins were negatively linked with BI because of degradation (>45%), with correlation coefficients ranging from 0.75 to 0.97. Furthermore, anthocyanidin reductase and laccase were the two key enzymes involved in the EB of WPs, with their activities increasing by 10.57-fold and 1.32-fold, respectively, with increasing drying temperature. A metabolic pathway network of the TRM was built to provide insights into the potential mechanisms underlying EB in WPs.PMID:39032301 | DOI:10.1016/j.foodchem.2024.140440

New Phytol. 2024 Jul 19. doi: 10.1111/nph.19977. Online ahead of print.ABSTRACTCananga odorata is known as a natural perfume tree of the Annonaceae family in Magnoliales. However, its phylogenetic position and the molecular mechanisms involved in the biosynthesis of the floral volatile organic compounds (VOCs) remain unclear. Here, by combining a variety of sequencing platforms, we present a telomere-to-telomere (T2T) genome of C. odorata with 735.83 Mb, which represents the highest integrity and assembly quality of genome in magnoliid plants reported to date. Phylogenetic analysis based on multiple datasets and approaches showed that C. odorata, as a member of magnoliids, is sister to eudicots, after their divergence from monocots. Metabolomic of VOCs in the essential oil and flowers scent showed that sesquiterpenes, especially β-caryophyllene, were the major compounds. Two CoTPS21 homologues derived from tandem duplication events were highly expressed during flower development and were identified as the key sesquiterpene synthases for the production of β-caryophyllene. In addition, CoSPL3 and CoSPL9 were considered as potential transcription factors for activating the expression of CoTPS21 homologues. Our results shed light on the molecular mechanisms underlying the biosynthesis of the unique floral fragrance in C. odorata and provide new insights into the phylogenetic position of magnoliids.PMID:39031984 | DOI:10.1111/nph.19977

J Sep Sci. 2024 Jun;47(12):e2400208. doi: 10.1002/jssc.202400208.ABSTRACTTraditional Chinese medicine (TCM) has garnered significant scientific interest in healthcare but faces increased regulatory scrutiny due to concerns about uncontrolled usage. This study focuses on characterizing Pogostemon cablin (PC) to mitigate potential misuse and identify chemotype differences. Leveraging untargeted metabolomics, we identified 222 distinctive features effectively differentiating PC from Agastache rugosa (AR), reducing misidentification risks. Pogostone and tilianin emerged as potential markers, leading to a high-performance liquid chromatography-diode array detection (HPLC-DAD) method development for PC and AR discrimination. Evaluation of PC chromatograms revealed notable profile and pogostone level differences among samples, suggesting chemotype associations. Untargeted metabolic profiling identified 78 features with significant differences, highlighting 7,3',4'-tri-O-methyleriodictyol as a potential discriminatory marker between PC chemotypes. The developed HPLC-DAD method quantified pogostone and 7,3',4'-tri-O-methyleriodictyol, effectively discriminating PC chemotypes. This platform differentiates PC and AR and distinguishes chemical types within PC, like pogostone-type and patchoulol-type. Applied to local TCM stores, it ensures PC authenticity. This approach addresses TCM control concerns, enhancing understanding and application of herbal medicine by providing insights into PC chemical composition and discrimination.PMID:39031742 | DOI:10.1002/jssc.202400208

Immun Inflamm Dis. 2024 Jul;12(7):e1315. doi: 10.1002/iid3.1315.ABSTRACTBACKGROUND: Asthma is routinely treated with inhaled corticosteroids (ICS). Asthma patients on ICS are at increased risk of adrenal suppression, a potentially serious effect of long-term glucocorticoid exposure; however, this relationship is poorly understood. Therefore, this study aims to identify metabolite biomarkers related to adrenal suppression in asthma patients taking ICS.METHODS: A total of 571 urine metabolites from 200 children with asthma on ICS in the Pharmacogenetics of Adrenal Suppression with Inhaled Steroids (PASS) cohort were profiled. Samples were grouped by peak plasma cortisol measurement as adrenal sufficient (>350 nmol/L) or insufficient (≤350 nmol/L) (outcome). Regression and discriminant-based statistical models combined with network analyses were utilized to assess relationships between metabolites and the outcome. Finally, prioritized metabolites were validated using data from an ancillary study of the Childhood Asthma Management (CAMP) cohort with similar characteristics to PASS.RESULTS: Ninety metabolites were significantly associated with adrenal suppression, of which 57 also could discriminate adrenal status. While 26 metabolites (primarily steroids) were present at lower levels in the adrenal insufficient patients, 14 were significantly elevated in this group; the top metabolite, mannitol/sorbitol, was previously associated with asthma exacerbations. Network analyses identified unique clusters of metabolites related to steroids, fatty acid oxidation, and nucleoside metabolism, respectively. Four metabolites including urocanic acid, acetylcarnitine, uracil, and sorbitol were validated in CAMP cohort for adrenal suppression.CONCLUSIONS: Urinary metabolites differ among asthma patients on ICS, by adrenal status. While steroid metabolites were reduced in patients with poor adrenal function, our findings also implicate previously unreported metabolites involved in amino acid, lipid, and nucleoside metabolism.PMID:39031511 | DOI:10.1002/iid3.1315

Plant Biotechnol J. 2024 Jun 21. doi: 10.1111/pbi.14402. Online ahead of print.ABSTRACTDrought stress substantially impacts crop physiology resulting in alteration of growth and productivity. Understanding the genetic and molecular crosstalk between stress responses and agronomically important traits such as fibre yield is particularly complicated in the allopolyploid species, upland cotton (Gossypium hirsutum), due to reduced sequence variability between A and D subgenomes. To better understand how drought stress impacts yield, the transcriptomes of 22 genetically and phenotypically diverse upland cotton accessions grown under well-watered and water-limited conditions in the Arizona low desert were sequenced. Gene co-expression analyses were performed, uncovering a group of stress response genes, in particular transcription factors GhDREB2A-A and GhHSFA6B-D, associated with improved yield under water-limited conditions in an ABA-independent manner. DNA affinity purification sequencing (DAP-seq), as well as public cistrome data from Arabidopsis, were used to identify targets of these two TFs. Among these targets were two lint yield-associated genes previously identified through genome-wide association studies (GWAS)-based approaches, GhABP-D and GhIPS1-A. Biochemical and phylogenetic approaches were used to determine that GhIPS1-A is positively regulated by GhHSFA6B-D, and that this regulatory mechanism is specific to Gossypium spp. containing the A (old world) genome. Finally, an SNP was identified within the GhHSFA6B-D binding site in GhIPS1-A that is positively associated with yield under water-limiting conditions. These data lay out a regulatory connection between abiotic stress and fibre yield in cotton that appears conserved in other systems such as Arabidopsis.PMID:39031479 | DOI:10.1111/pbi.14402

J Alzheimers Dis. 2024 Jul 19. doi: 10.3233/JAD-240654. Online ahead of print.ABSTRACTBACKGROUND: Among preventive strategies against dementia, nutrition is considered a powerful one and the recently established "nutritional cognitive neuroscience of aging" is a highly active research field.OBJECTIVE: The present study was designed to deeply characterize older adults across the continuum from cognitive integrity to mild cognitive impairment (MCI) and better elucidate the prognostic role of lipophilic micronutrients within their lipidomic signature.METHODS: 123 participants older than 65 years across the continuum from cognitive integrity to MCI were included [49 with subjective cognitive impairment, 29 women, 72.5±5.4 years, 26 MCI, 9 women, 74.5±5.8 years and 50 without cognitive impairment, 21 women, 70.8±4.3 years]. All participants underwent neuropsychological and nutritional examination as well as comprehensive geriatric assessment with calculation of the Multidimensional Prognostic Index (MPI) as a proxy of frailty and biological age and blood withdrawal for the analyses of lipophilic micronutrients, metabolomics and oxylipidomics. One year after the evaluation, same tests are ongoing.RESULTS: After adjustment for age, sex, daily fruit and vegetable intake and cholesterol, we found a significant positive correlation between lutein and the number of correct words in category fluency (p = 0.016).CONCLUSIONS: This result supports the importance of carotenoids as robust biomarkers of cognitive performance independent of the nutritional status and frailty of the participants, as the entire present study collective was robust (MPI 0-0.33). The complete analyses of the metabolome and the oxylipidome will hopefully shed light on the metabolic and prognostic signature of cognitive decline in the rapidly growing population at risk of frailty.PMID:39031373 | DOI:10.3233/JAD-240654

Med Oncol. 2024 Jul 20;41(8):203. doi: 10.1007/s12032-024-02440-3.ABSTRACTExosomes play a key role in colorectal cancer (CRC) related processes. This review explores the various functions of exosomes in CRC and their potential as diagnostic markers, therapeutic targets, and drug delivery vehicles. Exosomal long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) significantly influence CRC progression. Specific exosomal lncRNAs are linked to drug resistance and tumor growth, respectively, highlighting their therapeutic potential. Similarly, miRNAs like miR-21, miR-10b, and miR-92a-3p, carried by exosomes, contribute to chemotherapy resistance by altering signaling pathways and gene expression in CRC cells. The review also discusses exosomes' utility in CRC diagnosis. Exosomes from cancer cells have distinct molecular signatures compared to healthy cells, making them reliable biomarkers. Specific exosomal lncRNAs (e.g., CRNDE-h) and miRNAs (e.g., miR-17-92a) have shown effectiveness in early CRC detection and monitoring of treatment responses. Furthermore, exosomes show promise as vehicles for targeted drug delivery. The potential of mesenchymal stem cell (MSC)-derived exosomes in CRC treatment is also noted, with their role varying from promoting to inhibiting tumor progression. The application of multi-omics approaches to exosome research is highlighted, emphasizing the potential for discovering novel CRC biomarkers through comprehensive genomic, transcriptomic, proteomic, and metabolomic analyses. The review also explores the emerging field of exosome-based vaccines, which utilize exosomes' natural properties to elicit strong immune responses. In conclusion, exosomes represent a promising frontier in CRC research, offering new avenues for diagnosis, treatment, and prevention. Their unique properties and versatile functions underscore the need for continued investigation into their clinical applications and underlying mechanisms.PMID:39031221 | DOI:10.1007/s12032-024-02440-3

J Exp Bot. 2024 Jul 20:erae311. doi: 10.1093/jxb/erae311. Online ahead of print.ABSTRACTThe plant cuticle is a complex extracellular lipid barrier that has multiple protective functions. We investigated cuticle deposition by integrating metabolomics and transcriptomics data gathered from six different maize seedling organs of four genotypes, the inbred lines B73 and Mo17, and their reciprocal hybrids. These datasets captured the developmental transition of the seedling from heterotrophic skotomorphogenic growth to autotrophic photomorphogenic growth, which is a transition that is highly vulnerable to environmental stresses. Statistical interrogation of these data reveals that the predominant determinant of cuticle composition is seedling organ type, whereas the seedling genotype has a smaller effect on this phenotype. Gene-to-metabolite associations assessed by integrated statistical analyses identified three gene networks connected with the deposition of different elements of the cuticle: a) cuticular waxes; b) monomers of lipidized cell wall biopolymers, including cutin and suberin; and c) both of these elements. These gene networks reveal three metabolic programs that appear to support cuticle deposition, including processes of chloroplast biogenesis, lipid metabolism, and molecular regulation (e.g., transcription factors, post-translational regulators and phytohormones). This study demonstrates the wider physiological metabolic context that can determine cuticle deposition and lays the groundwork for new targets for modulating properties of this protective barrier.PMID:39031128 | DOI:10.1093/jxb/erae311

FEBS Open Bio. 2024 Jul 19. doi: 10.1002/2211-5463.13860. Online ahead of print.ABSTRACTEpithelial-to-mesenchymal transition (EMT) contributes to the poor prognosis of patients with cancer by promoting distant metastasis and anti-cancer drug resistance. Several distinct metabolic alterations have been identified as key EMT phenotypes. In the present study, we further characterize the role of transforming growth factor-β (TGF-β)-induced EMT in non-small-cell lung cancer. Our study revealed that TGF-β plays a role in EMT functions by upregulation of cytidine 5'-triphosphate synthetase 1 (CTPS), a vital enzyme for CTP biosynthesis in the pyrimidine metabolic pathway. Both knockdown and enzymatic inhibition of CTPS reduced TGF-β-induced changes in EMT marker expression, chemoresistance and migration in vitro. Moreover, CTPS knockdown counteracted the TGF-β-mediated downregulation of UDP-glucuronate, glutarate, creatine, taurine and nicotinamide. These findings indicate that CTPS plays a multifaceted role in EMT metabolism, which is crucial for the malignant transformation of cancer through EMT, and underline its potential as a promising therapeutic target for preventing drug resistance and metastasis in non-small-cell lung cancer.PMID:39030877 | DOI:10.1002/2211-5463.13860

Chembiochem. 2024 Jul 18:e202400398. doi: 10.1002/cbic.202400398. Online ahead of print.ABSTRACTMarine-derived fungi have emerged as a source for novel metabolites with a broad range of bioactivities. However, accessing the full potential of fungi under standard laboratory conditions remains challenging. LC-MS-based metabolomics in combination with varied culture conditions is a fast and powerful tool to detect new metabolites. Here, three developmental forms of the marine-derived fungus Aspergillus alliaceus were analyzed and 14 fungal metabolites, including new brominated polyketides (11-14) were isolated. Structure elucidation relied mainly on 1D and 2D NMR techniques and was supported by low- and high-resolution mass spectrometry and DFT-based computations. We sequenced the A. alliaceus genome, identified the bianthrone-producing biosynthetic gene cluster, and conducted expression analysis on genes involved in sexual development and biosynthesis. The NCI-60 cell line panel revealed selective in vitro activity against triple-negative breast cancer (TNBC) for the halogenated allianthrones and their full anti-proliferative and cytotoxic effects were evaluated in five TNBC cell lines.PMID:39030818 | DOI:10.1002/cbic.202400398

J Appl Toxicol. 2024 Jul 18. doi: 10.1002/jat.4669. Online ahead of print.ABSTRACTBile acid homeostasis is crucial for the normal physiological functioning of the liver. Disruptions in bile acid profiles are closely linked to the occurrence of cholestatic liver injury. As part of our diagnostic and therapeutic approach, we aimed to investigate the disturbance in bile acid profiles during cholestasis and its correlation with cholestatic liver injury. Before the occurrence of liver injury, alterations in bile acid profiles were detected in both plasma and liver between 8 and 16 h, persisting up to 96 h. TCA, TCDCA, and TUDCA in the plasma, as well as TCA, TUDCA, TCDCA, TDCA, TLCA, and THDCA in the liver, emerged as early sensitive and potential markers for diagnosing ANIT-induced cholestasis at 8-16 h. The distinguishing features of ANIT-induced liver injury were as follows: T-BAs exceeding G-BAs and serum biochemical indicators surpassing free bile acids. Notably, plasma T-BAs, particularly TCA, exhibited higher sensitivity to cholestatic hepatotoxicity compared with serum enzyme activity and liver histopathology. Further investigation revealed that TCA exacerbated ANIT-induced liver injury by elevating liver function enzyme activity, inflammation, and bile duct proliferation and promoting the migration of bile duct epithelial cell. Nevertheless, no morphological changes or alterations in transaminase activity indicative of liver damage were observed in the rats treated with TCA alone. Additionally, there were no changes in bile acid profiles or inflammatory responses under physiological conditions with maintained bile acid homeostasis. In summary, our findings suggest that taurine-conjugated bile acids in both plasma and liver, particularly TCA, can serve as early and sensitive markers for predicting intrahepatic cholestatic drugs and can act as potent exacerbators of cholestatic liver injury progression. However, exogenous TCA does not induce liver injury under physiological conditions where bile acid homeostasis is maintained.PMID:39030796 | DOI:10.1002/jat.4669

ISME J. 2024 Jul 20:wrae137. doi: 10.1093/ismejo/wrae137. Online ahead of print.ABSTRACTClimate change-driven sea level rise threatens freshwater ecosystems and elicits salinity stress in microbiomes. Methane emissions in these systems are largely mitigated by methane-oxidizing microorganisms. Here, we characterized the physiological and metabolic response of freshwater methanotrophic archaea to salt stress. In our microcosm experiments, inhibition of methanotrophic archaea started at 1%. However, during gradual increase of salt up to 3% in a reactor over 12 weeks, the culture continued to oxidize methane. Using gene expression profiles and metabolomics, we identified a pathway for salt-stress response that produces the osmolyte of anaerobic methanotrophic archaea: N(ε)-acetyl-β-L-lysine. An extensive phylogenomic analysis on N(ε)-acetyl-β-L-lysine-producing enzymes revealed that they are widespread across both bacteria and archaea, indicating a potential horizontal gene transfer and a link to BORG extrachromosomal elements. Physicochemical analysis of bioreactor biomass further indicated the presence of sialic acids and the consumption of intracellular polyhydroxyalkanoates in anaerobic methanotrophs during salt stress.PMID:39030685 | DOI:10.1093/ismejo/wrae137

Biotechnol Biofuels Bioprod. 2024 Jul 19;17(1):106. doi: 10.1186/s13068-024-02556-8.ABSTRACTBACKGROUND: Trichoderma reesei is known for its ability to produce large amounts of extracellular proteins and is one of the most important industrially used filamentous fungus. Xylanase regulator 1 (XYR1) is the master regulator responsible for the activation of cellulase and hemicellulase gene expression under inducing conditions. It has been reported that strains with point mutations in certain areas of xyr1 bypass the need for inducing carbon source, allowing high (hemi)cellulase production even in the presence of glucose. These mutations also change the profile of produced proteins, shifting it more towards xylanase production, and increase the overall protein production in inducing conditions. However, how these mutations alter the metabolism and other cellular processes to cause these changes remains unclear.RESULTS: In this study, we aimed to explore changes caused by a point mutation in xyr1 on transcriptomic and metabolic level to better understand the reasons behind the increased protein production in both repressing glucose and inducing lactose conditions. As expected, the expression of many carbohydrate-active enzyme (CAZy) genes was increased in the xyr1 mutant in both conditions. However, their induction was higher under inducing conditions. The xyr1 mutant strain built more biomass and produced more extracellular proteins during growth on lactose compared to the wild type xyr1 strain. Genes involved in oxidoreductive D-galactose catabolism pathway were upregulated in the xyr1 mutant strain, potentially contributing to the more efficient utilization of lactose. In addition to CAZy genes, clustering and enrichment analysis showed over-representation of mitochondria-related Gene Ontology terms in clusters where gene expression was higher in the xyr1 mutant, indicating that mitochondria play a role in the altered metabolic state associated with the xyr1 mutation. Metabolomics revealed that free tyrosine was more abundant in the xyr1 mutant strain in all measured timepoints, whereas multiple fatty acids were less abundant in the mutant strain on glucose.CONCLUSIONS: The results contribute to more in-depth knowledge on T. reesei physiology growing under inducing and repressing carbon sources and gives new insights on the function of the master regulator XYR1. The vast data generated serve as a source for new targets for improved protein production.PMID:39030601 | DOI:10.1186/s13068-024-02556-8

Microbiome. 2024 Jul 19;12(1):131. doi: 10.1186/s40168-024-01844-7.ABSTRACTBACKGROUND: The average daily gain (ADG) of preweaning calves significantly influences their adult productivity and reproductive performance. Gastrointestinal microbes are known to exert an impact on host phenotypes, including ADG. The aim of this study was to investigate the mechanisms by which gastrointestinal microbiome regulate ADG in preweaning calves and to further validate them by isolating ADG-associated rumen microbes in vitro.RESULTS: Sixteen Holstein heifer calves were selected from a cohort with 106 calves and divided into higher ADG (HADG; n = 8) and lower ADG (LADG; n = 8) groups. On the day of weaning, samples of rumen contents, hindgut contents, and plasma were collected for rumen metagenomics, rumen metabolomics, hindgut metagenomics, hindgut metabolomics, and plasma metabolomics analyses. Subsequently, rumen contents of preweaning Holstein heifer calves from the same dairy farm were collected to isolate ADG-associated rumen microbes. The results showed that the rumen microbes, including Pyramidobacter sp. C12-8, Pyramidobacter sp. CG50-2, Pyramidobacter porci, unclassified_g_Pyramidobacter, Pyramidobacter piscolens, and Acidaminococcus fermentans, were enriched in the rumen of HADG calves (LDA > 2, P < 0.05). Enrichment of these microbes in HADG calves' rumen promoted carbohydrate degradation and volatile fatty acid production, increasing proportion of butyrate in the rumen and ultimately contributing to higher preweaning ADG in calves (P < 0.05). The presence of active carbohydrate degradation in the rumen was further suggested by the negative correlation of the rumen microbes P. piscolens, P. sp. C12-8 and unclassified_g_Pyramidobacter with the rumen metabolites D-fructose (R < - 0.50, P < 0.05). Widespread positive correlations were observed between rumen microbes (such as P. piscolens, P. porci, and A. fermentans) and beneficial plasma metabolites (such as 1-pyrroline-5-carboxylic acid and 4-fluoro-L-phenylalanine), which were subsequently positively associated with the growth rate of HADG calves (R > 0.50, P < 0.05). We succeeded in isolating a strain of A. fermentans from the rumen contents of preweaning calves and named it Acidaminococcus fermentans P41. The in vitro cultivation revealed its capability to produce butyrate. In vitro fermentation experiments demonstrated that the addition of A. fermentans P41 significantly increased the proportion of butyrate in the rumen fluid (P < 0.05). These results further validated our findings. The relative abundance of Bifidobacterium pseudolongum in the hindgut of HADG calves was negatively correlated with hindgut 4-hydroxyglucobrassicin levels, which were positively correlated with plasma 4-hydroxyglucobrassicin levels, and plasma 4-hydroxyglucobrassicin levels were positively correlated with ADG (P < 0.05).CONCLUSIONS: This study's findings unveil that rumen and hindgut microbes play distinctive roles in regulating the preweaning ADG of Holstein heifer calves. Additionally, the successful isolation of A. fermentans P41 not only validated our findings but also provided a valuable strain resource for modulating rumen microbes in preweaning calves. Video Abstract.PMID:39030599 | DOI:10.1186/s40168-024-01844-7

BMC Genomics. 2024 Jul 19;25(1):706. doi: 10.1186/s12864-024-10608-4.ABSTRACTBACKGROUND: According to Chinese ancient books, both fruits and rhizomes of Polygonatum cyrtonema Hua have medicinal and edible values. Up to now, there is no report about the metabolite profiles and regulatory network in fruits and different year-old rhizomes of P. cyrtonema.RESULTS: In this study, we performed integrative analyses of metabolome and transcriptome to reveal the dynamic accumulation and regulatory network of fruits and different year-old rhizomes in P. cyrtonema. The relative content of phenolic acids, lignans and coumarins, flavonoids and alkaloids increased with growth years, while steroids and lipids decreased with it. In addition, the relative content of nucleotides and derivatives, flavonoids, organic acids, steroids and lipids in fruits were higher than rhizomes. Genes that might relate to the biosynthesis of polysaccharides, flavonoids, triterpene saponins and alkaloids biosynthesis were further analyzed by transcriptome analysis, including sacA, GMPP, PMM, CCoAOMT, CHI, ANR, CHS, DXS, GGPS, ZEP, CYP72A219 and so on, for their expressions were positively correlated with the relative content of the metabolites. Additionally, the correlation network in sugar and aromatic amino acids metabolites were constructed to further illustrate the biosynthesis of polysaccharides, flavonoids and alkaloids in P. cyrtonema, and some transcription factors (TFs) were screened, such as C2C2, MYB, bZIP, GRAS and NAC.CONCLUSIONS: This study can deepen our understanding of the accumulation patterns and molecular mechanism of the main compounds in P. cyrtonema, and provide reference for the standardize production of P. cyrtonema.PMID:39030489 | DOI:10.1186/s12864-024-10608-4

Int J Legal Med. 2024 Jul 20. doi: 10.1007/s00414-024-03288-y. Online ahead of print.NO ABSTRACTPMID:39030382 | DOI:10.1007/s00414-024-03288-y

Commun Biol. 2024 Jul 19;7(1):880. doi: 10.1038/s42003-024-06470-5.ABSTRACTThe role of hormones in gut-brain crosstalk is largely elusive, but recent research supports specific changes in hormone levels correlated with the gut microbiota. An interesting but unstudied area in microbial endocrinology is the interplay between the microbiota and sex hormones. The aim of this study is to investigate the effect of testosterone and sex on the mouse gut microbiome. We use in vitro experiments to test direct effects of testosterone on bacteria in fecal samples collected from male and female mice pre- and post-puberty. Sex-specific microbial and metabolic differences surrounding puberty are also examined in vivo. We then explore effects of testosterone supplementation in vivo, characterizing microbiota and metabolomes of male and female mice. We detect sex-specific differences in microbiota and associated metabolites of mice post-puberty, but in vitro experiments reveal that testosterone only affects microbiota of fecal samples collected before puberty. Testosterone supplementation in vivo affects gut microbiota and metabolomes in both male and female mice. Taking our results from in vitro and in vivo experiments, we conclude that the shift in the microbiome after puberty is at least partially caused by the higher levels of sex hormones, mainly testosterone, in the host.PMID:39030253 | DOI:10.1038/s42003-024-06470-5

Anal Chim Acta. 2024 Aug 15;1317:342913. doi: 10.1016/j.aca.2024.342913. Epub 2024 Jun 26.ABSTRACTBACKGROUND: Lipidomics studies require rapid separations with accurate and reliable quantification results to further elucidate the role of lipids in biological processes and their biological functions. Supercritical fluid chromatography (SFC), in particular, can provide this rapid and high-resolution separation. The combination with trapped ion mobility spectrometry (TIMS) has not yet been applied, although the post-ionization separation method in combination with liquid chromatography or imaging techniques has already proven itself in resolving isomeric and isobaric lipids and preventing false identifications. However, a multidimensional separation method should not only allow confident identification but also provide quantitative results to substantiate studies with absolute concentrations.RESULTS: A SFC method was developed and the hyphenation of SFC and TIMS was further explored towards the separation of different isobaric overlaps. Furthermore, lipid identification was performed using mass spectrometry (MS) and parallel accumulation serial fragmentation (PASEF) MS/MS experiments in addition to retention time and collision cross section (CCS). Quantification was further investigated with short TIMS ramps and performed based on the ion mobility signal of lipids, since TIMS increases the sensitivity by noise filtering. The final method was, as an exemplary study, applied to investigate the function of different ceramide synthases (CerS) in the nematode and model organism Caenorhabditis elegans (C. elegans). Loss of three known CerS hyl-1, hyl-2 and lagr-1 demonstrated different influences on and alterations in the sphingolipidome.SIGNIFICANCE: This method describes for the first time the combination of SFC and TIMS-MS/MS, which enables a fast and sensitive quantification of lipids. The results of the application to C. elegans samples prove the functionality of the method and support research on the metabolism of sphingolipids in nematodes.PMID:39030025 | DOI:10.1016/j.aca.2024.342913