PubMed

J Immunother Cancer. 2023 Nov;11(11):e007805. doi: 10.1136/jitc-2023-007805.ABSTRACTBACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Despite the successful application of immune checkpoint blockade in a range of human cancers, immunotherapy in PDAC remains unsuccessful. PDAC is characterized by a desmoplastic, hypoxic and highly immunosuppressive tumor microenvironment (TME), where T-cell infiltration is often lacking (immune desert), or where T cells are located distant from the tumor islands (immune excluded). Converting the TME to an immune-inflamed state, allowing T-cell infiltration, could increase the success of immunotherapy in PDAC.METHOD: In this study, we use the KPC3 subcutaneous PDAC mouse model to investigate the role of tumor-derived sialic acids in shaping the tumor immune landscape. A sialic acid deficient KPC3 line was generated by genetic knock-out of the CMAS (cytidine monophosphate N-acetylneuraminic acid synthetase) enzyme, a critical enzyme in the synthesis of sialic acid-containing glycans. The effect of sialic acid-deficiency on immunotherapy efficacy was assessed by treatment with anti-programmed cell death protein 1 (PD-1) and agonistic CD40.RESULT: The absence of sialic acids in KPC3 tumors resulted in increased numbers of CD4+ and CD8+ T cells in the TME, and reduced frequencies of CD4+ regulatory T cells (Tregs) within the T-cell population. Importantly, CD8+ T cells were able to infiltrate the tumor islands in sialic acid-deficient tumors. These favorable alterations in the immune landscape sensitized sialic acid-deficient tumors to immunotherapy, which was ineffective in sialic acid-expressing KPC3 tumors. In addition, high expression of sialylation-related genes in human pancreatic cancer correlated with decreased CD8+ T-cell infiltration, increased presence of Tregs, and poorer survival probability.CONCLUSION: Our results demonstrate that tumor-derived sialic acids mediate T-cell exclusion within the PDAC TME, thereby impairing immunotherapy efficacy. Targeting sialic acids represents a potential strategy to enhance T-cell infiltration and improve immunotherapy outcomes in PDAC.PMID:37940346 | DOI:10.1136/jitc-2023-007805

Carbohydr Polym. 2024 Jan 1;323:121422. doi: 10.1016/j.carbpol.2023.121422. Epub 2023 Sep 20.ABSTRACTAlginate oligosaccharides (AOS) have various biological activities in the regulation of plant growth and development. However, little is known about the effect on fruit coloration. We assessed the impacts of varying Mannuronate/Guluronate ratio (M/G ratios) of AOS, namely oligoguluronate (GAOS), oligomannuronate (MAOS), and heterogeneous AOS (HAOS), and delved into the structure-function relationship, as well as the mechanisms of regulation. The promotion of strawberry coloration was observed in HAOS (M/G ratio ≈ 1.58; Mw = 2800 Da) and MAOS (M/G ratio ≈ 6.77; Mw = 6000 Da), whereas GAOS (M/G ratio ≈ 0.2; Mw = 5500 Da) did not exhibit any significant effect. The metabolomics analysis revealed that the impact of AOS was predominantly observed on the biosynthesis of flavonoids. The predominant flavonoids present in strawberries were anthocyanins. The application of HAOS and MAOS on strawberries increased anthocyanin content. This was accompanied by an up-regulation of genes related to the JA synthesis pathway. Additionally, transcription factors and structural genes related to anthocyanin synthesis and transport were up-regulated. The findings suggest that HAOS and MAOS may trigger the JA pathway, leading to an elevation in anthocyanin metabolism and consequent enhancement of strawberry coloration.PMID:37940253 | DOI:10.1016/j.carbpol.2023.121422

Sci Total Environ. 2023 Nov 6:168290. doi: 10.1016/j.scitotenv.2023.168290. Online ahead of print.ABSTRACTMicrocystis aeruginosa is ubiquitously found in various water bodies and can produce microcystins (MCs), which threaten the health of aquatic animals and human beings. The elimination of excessive M. aeruginosa is beneficial for the protection of the ecosystems and public health. In this regard, algae-lysing bacteria have been extensively studied as an effective measure for their eradication. However, the active substances generated by algae-lysing bacteria are limited. For this study, we reveal that the phenyllactic acid (PLA) produced by Leuconostoc mesenteroides DH exhibits high efficacy for the removal of M. aeruginosa, and explore its underlying mechanism. It was found that a cell-free supernatant of strain DH possessed high removal activities against M. aeruginosa. Abundant reactive oxygen species were induced in algal cells following exposure to strain DH supernatant, as well as superoxide dismutase and catalase responses. Furthermore, the integrity of algal cell membranes and photosynthesis was seriously damaged. Interestingly, added exogenous eugenol significantly inhibited the synthesis of active substance produced by strain DH, which further identified PLA as the active substance that contributes to the eradication of M. aeruginosa on the basis of metabolomics analysis. Our finding demonstrated, for the first time, that PLA (as an anti-cyanobacterial compound) can be used for the removal of M. aeruginosa, which provides a theoretical basis for the control of M. aeruginosa.PMID:37939934 | DOI:10.1016/j.scitotenv.2023.168290

Transplant Cell Ther. 2023 Nov 6:S2666-6367(23)01672-X. doi: 10.1016/j.jtct.2023.11.005. Online ahead of print.ABSTRACTAcute graft-versus-host disease (aGVHD) represents a fatal severe complication following allogeneic hematopoietic stem cell transplantation. As a promising cell therapeutic strategy of aGVHD, the mechanism of mesenchymal stem cells (MSC) to ameliorate aGVHD has not been fully clarified, especially in the field of intestinal homeostasis including the intestinal microbiome involved in the pathogenesis of aGVHD. The present study aimed to explore the effect of MSC on intestinal homeostasis including the intestinal barrier and intestinal microbiome and its metabolites as well as the role of intestinal microbiome in the preventive process of hAMSCs ameliorating aGVHD. The preventive effects of human amniotic membrane-derived MSC (hAMSCs) was assessed in humanized aGVHD models. Immunohistochemistry and RT-qPCR were used to evaluate intestinal barrier function. 16S rRNA sequencing and targeted metabolomics assay were performed to observe the alternation of intestinal microbiome and the amounts of medium-chain fatty acids (MCFAs) and short-chain fatty acids (SCFAs), respectively. Flow cytometer was performed to analyze the frequencies of T immune cells. Through animal experiments, we found that hAMSCs had the potential to prevent aGVHD. hAMSCs could repair the damage of intestinal barrier structure and function as well as improve the dysbiosis of intestinal microbiome induced by aGVHD, and meanwhile, upregulate the concentration of metabolites SCFAs, so as to reshape intestinal homeostasis. Gut microbiota depletion and fecal microbial transplantation confirmed the involvement of intestinal microbiome in the preventive process of hAMSCs on aGVHD. Our findings showed that hAMSCs prevented aGVHD in an intestinal microbiome-dependent manner, which might shed light on a new mechanism of hAMSCs inhibiting aGVHD and promote the development of new prophylaxis regimes for aGVHD prevention.PMID:37939900 | DOI:10.1016/j.jtct.2023.11.005

J Dairy Sci. 2023 Nov 6:S0022-0302(23)00782-8. doi: 10.3168/jds.2023-23876. Online ahead of print.ABSTRACTWe examined the effects of 2 multi-species direct-fed microbial (DFM) supplements on ruminal and plasma metabolome of early-lactation dairy cows using a high-coverage untargeted metabolomics approach. A total of 45 multiparous Holstein cows (41 ± 7 DIM) were enrolled for the 14-d pre-experimental and 91-d experimental period study, and were subset from a lactation performance study, which utilized a total of 114 cows. Cows were blocked using pre-experimental energy-corrected milk yield and randomly assigned within each block to 1 of 3 treatments: 1. Corn silage-based diet with no DFM supplement (Control; CON), 2. Basal diet top-dressed with mixture of Lactobacillus animalis and Propionibacterium freudenreichii at 3 × 109 cfu/day (PRO-A), and 3. Basal diet top-dressed with a mixture of L. animalis, P. freudenreichii, Bacillus subtilis, and B. licheniformis at 11.8 × 109 cfu/day (PRO-B). The basal diet was fed ad libitum daily as a total mixed ration at 0600 and 1200 h for a total duration of 91 d. Rumen fluid and blood samples were taken on d -3, 28, 49, 70, and 91, and immediately stored at -80°C. Before analysis, ruminal and plasma samples from d 28, 49, 70, and 91 were composited. In-depth untargeted metabolome profile of the composite rumen and plasma samples and the d -3 samples was done using a chemical isotope labeling (CIL)/liquid chromatography-mass spectrometry (LC-MS)-based technique. Differentially abundant metabolites (fold change (FC) values ≥1.2 or ≤0.83 and false discovery rate (FDR)-adjusted P-value ≤0.05) were identified with a Volcano plot. In the rumen, compared with CON, supplemental PRO-A increased (FC ≥1.2; FDR ≤0.05) the relative concentrations of 9 metabolites including 2-hydroxy-2,4-pentadienoic acid, glutaric acid, quinolinic acid, and shikimic acid, while PRO-B increased relative concentrations of 16 metabolites including 2-hydroxy-2,4-pentadienoic acid, glutaric acid, 16-hydroxypalmitic acid, and 2 propionate precursors (succinic and methylsuccinic acids). Relative to PRO-A, supplemental PRO-B increased (FC ≥1.2; FDR ≤0.05) relative rumen concentrations of 3 metabolites: 16-hydroxypalmitic acid, indole-3-carboxylic acid, and 5-aminopentanoic acid, but reduced relative rumen concentrations of 13 metabolites including carnitine, threonic acid, and shikimic acid. Compared with CON, relative concentrations of 13 plasma metabolites including myxochelin A and glyceraldehyde were increased (FC ≥1.2; FDR ≤0.05) by PRO-A, whereas those of 9 plasma metabolites including 4-2-aminophenyl-2,4-dioxobutanoic acid, N-acetylornithine, and S-norlaudanosolin were reduced (FC ≤0.83; FDR ≤0.05). Supplemental PRO-B increased (FC ≥1.2; FDR ≤0.05) relative concentrations of 9 plasma metabolites including trans-o-hydroxybenzylidenepyruvic acid and 3-methylsalicylaldehyde, while reducing relative concentrations of 4 plasma metabolites including β-ethynylserine and kynurenine. Pathway analysis of the differentially abundant metabolites in both rumen and plasma revealed that these metabolites were involved in amino acid and fatty acid metabolisms and have antimicrobial and immune-stimulating properties. The results of this study demonstrated that dietary supplementation of either PRO-A or PRO-B altered plasma and ruminal metabolome. Notably, ruminal and plasma metabolites involved in the metabolism of amino acids and fatty acids and those with immunomodulatory properties were altered by either or both of the 2 microbial additives.PMID:37939839 | DOI:10.3168/jds.2023-23876

J Dairy Sci. 2023 Nov 6:S0022-0302(23)00786-5. doi: 10.3168/jds.2023-24135. Online ahead of print.ABSTRACTThis study evaluated 75 strains of lactic acid bacteria (LAB) isolated from traditional dairy products in western China for their probiotic properties. Among them, Limosilactobacillus fermentum WXZ 2-1, Lactiplantibacillus plantarum TXZ 2-35, Companilactobacillus crustorum QHS 9, and Companilactobacillus crustorum QHS 10 demonstrated potential probiotic characteristics. The antioxidant capacity of these 4 strains was assessed, revealing that L. fermentum WXZ 2-1 exhibited the highest antioxidant capacity. Furthermore, when cocultured with Streptococcus salivarius ssp. thermophiluss and Lactobacillus delbrueckii ssp. bulgaricus, L. fermentum WXZ 2-1 demonstrated a synergistic effect in growth medium and goat milk. To explore its impact on goat milk fermentation, different amounts of L. fermentum WXZ 2-1 were added to goat milk, and its physicochemical properties, antioxidant activity, flavor substances, and metabolomics were analyzed. The study found that the incorporation of L. fermentum WXZ 2-1 in goat milk fermentation significantly improved the texture characteristics, antioxidant capacity, and flavor of fermented goat milk. These findings highlight the potential of L. fermentum WXZ 2-1 as a valuable probiotic strain for enhancing the functionality and desirability of fermented goat milk, contributing to the development of novel functional foods with improved health benefits and enhanced quality attributes.PMID:37939838 | DOI:10.3168/jds.2023-24135

Plant Physiol Biochem. 2023 Nov 1;205:108157. doi: 10.1016/j.plaphy.2023.108157. Online ahead of print.ABSTRACTTea is one of the most popular beverages, it has many health benefits and flavor properties due to the presence of numerous secondary metabolites. Camellia assamica is also a main source of tea, which is mainly planted in the regions of southwest China. In this study, a non-targeted and targeted metabolomics analysis and sensory evaluation on tea leaves with and without mistletoe (Viscum articulatum) was carried out using liquid chromatography-mass spectrometry. RNA-seq-based transcriptomic analysis was conducted in parallel on the same samples, subsequently gene expression and metabolic differentiation were also investigated. Tea leaves with mistletoe presented much lower contents of (-)-catechin, (-)-epicatechin, (-)-gallocatechin gallate and (-)-epicatechin gallate, but significantly higher levels of free amino acids including Arg, Asp, GABA and Gln than that without mistletoe. Transcriptomic analysis also confirmed the main differentially expressed genes (DEGs) containing phenylpropanoid and flavonoid biosynthesis were down-regulated, but genes of amino acid biosynthesis were up-regulated. qRT-PCR analysis further revealed that the relative expression of CsCHS, CsC4H, CsANS, CsLAR, and CsF3H was hindered, while CsglyA and CsilvE expression was increased.PMID:37939544 | DOI:10.1016/j.plaphy.2023.108157

Biosens Bioelectron. 2023 Oct 23;244:115780. doi: 10.1016/j.bios.2023.115780. Online ahead of print.ABSTRACTMetabolome analysis has gained widespread application in disease diagnosis owing to its ability to provide comprehensive information, including disease phenotypes. In this study, we utilized 3D superstructures fabricated through evaporation-induced microprinting to analyze the metabolome for glaucoma diagnosis. 3D superstructures offer the following advantages: high hotspot density per unit volume of the structure extending from two to three dimensions, excellent signal repeatability due to the reproducibility and defect tolerance of 3D printing, and high thermal stability due to the PVP-enclosed capsule form. Leveraging the superior optical properties of the 3D superstructure, we aimed to classify patients with glaucoma. The signal obtained from the 3D superstructure was employed in a Deep Neural Network (DNN) classification model to accurately classify glaucoma patients. The sensitivity and specificity of the model were determined as 92.05% and 93.51%, respectively. Additionally, the fabrication of 3D superstructures can be performed at any stage, significantly reducing measurement time. Furthermore, their thermal stability allows for the analysis of smaller samples. One notable advantage of 3D superstructures is their versatility in accommodating different target materials. Consequently, they can be utilized for a wide range of metabolic analyses and disease diagnoses.PMID:37939415 | DOI:10.1016/j.bios.2023.115780

Hear Res. 2023 Nov 4;440:108913. doi: 10.1016/j.heares.2023.108913. Online ahead of print.ABSTRACTAging is an inevitable phase in mammals that leads to health impairments, including hearing loss. Age-related hearing loss (AHL) leads to psychosocial problems and cognitive decline in the elderly. In this study, mean thresholds of auditory brainstem responses (ABR) and distortion-product otoacoustic emissions (DPOAE) increased at multiple frequencies in aged rats (14 months old) compared to young rats (2 months old). Using untargeted ultra-high performance liquid chromatography-mass spectroscopy (LC-MS), we quantified molecular metabolic markers in the cochlea of aged rats with hearing loss. A total of 137 different metabolites were identified in two groups, highlighting several prominent metabolic pathways related to purine metabolism; glycine, serine, and threonine metabolism; arginine and proline metabolism; and pyrimidine metabolism. In addition, the beneficial effects of purine supplementation were demonstrated in a mimetic model of senescent marginal cells (MCs). Overall, altered metabolic profiling is both the cause and manifestation of pathology, and our results suggest that cellular senescence and dysfunctional cochlear metabolism may contribute to the progression of AHL. These findings are seminal in elucidating the pathophysiological mechanisms underlying AHL and serve as a basis for future clinical predictions and interventions in AHL.PMID:37939412 | DOI:10.1016/j.heares.2023.108913

Anal Chem. 2023 Nov 8. doi: 10.1021/acs.analchem.3c02263. Online ahead of print.ABSTRACTCompound annotation using spectral-matching algorithms is vital for (MS/MS)-based metabolomics research, but is hindered by the lack of high-quality reference MS/MS library spectra. Finding and removing errors from libraries, including noise ions, is mostly done manually. This process is both error-prone and time-consuming. To address these challenges, we have developed an automated library curation pipeline, LibGen, to universally build novel spectral libraries. This pipeline corrects mass errors, denoises spectra by subformula assignments, and performs quality control of the reference spectra by calculating explained intensity and spectral entropy. We employed LibGen to generate three high-quality libraries with chemical standards of 2241 natural products. To this end, we used an IQ-X orbital ion trap mass spectrometer to generate 1947 classic high-energy collision dissociation spectra (HCD) as well as 1093 ultraviolet-photodissociation (UVPD) mass spectra. The third library was generated by an electron-activated collision dissociation (EAD) 7600 ZenoTOF mass spectrometer yielding 3244 MS/MS spectra. The natural compounds covered 140 chemical classes from prenol lipids to benzypyrans with >97% of the compounds showing <0.2 Tanimoto-similarity, demonstrating a very high structural variance. Mass spectra showed much higher information content for both UVPD- and EAD-mass spectra compared to classic HCD spectra when using spectral entropy calculations. We validated the denoising algorithm by acquiring MS/MS spectra at high concentration and at 13-fold diluted chemical standards. At low concentrations, a higher proportion of spectra showed apparent fragment ions that could not be explained by subformula losses of the parent molecule. When more than 10% of the total intensity of MS/MS fragments was regarded as noise ions, spectra were considered as low quality and were not included in the libraries. As the overall process is fully automated, LibGen can be utilized by all researchers who create or curate mass spectral libraries. The libraries we created here are publicly available at MassBank.us.PMID:37939222 | DOI:10.1021/acs.analchem.3c02263

PLoS One. 2023 Nov 8;18(11):e0281293. doi: 10.1371/journal.pone.0281293. eCollection 2023.ABSTRACTDrought is the single greatest abiotic factor influencing crop yield worldwide. Plants remain in one area for extended periods, making them vulnerable to natural and man-made influences. Understanding plant drought responses will help us develop strategies for breeding drought-resistant crops. Large proteome analysis revealed that leaf and root tissue proteins respond to drought differently depending on the plant's genotype. Commonly known as tomatoes, Solanum Lycopersicum is a globally important vegetable crop. However, drought stress is one of the most significant obstacles to tomato production, making the development of cultivars adapted to dry conditions an essential goal of agricultural biotechnology. Breeders have put quite a lot of time and effort into the tomato to increase its productivity, adaptability, and resistance to biotic and abiotic challenges. However, conventional tomato breeding has only improved drought resistance due to the complexity of drought traits. The resilience of tomatoes under drought stress has been the subject of extensive study. Using contemporary sequencing approaches like genomics, transcriptomics, proteomics, and metabolomics has dramatically aided in discovering drought-responsive genes. One of the most prominent families of plant transcription factors, WRKY genes, plays a crucial role in plant growth and development in response to natural and abiotic stimuli. To develop plants that can withstand both biotic and abiotic stress, understanding the relationships between WRKY-proteins (transcription factors) and other proteins and ligands in plant cells is essential. This is despite the fact that tomatoes have a long history of domestication. This research aims to utilize Lupenone, a hormone produced in plant roots in response to stress, to increase drought resistance in plants. Lupenone exhibits a strong affinity for the WRKY protein at -9.64 kcal/mol. Molecular docking and modeling studies show that these polyphenols have a significant role in making Solanum Lycopersicum drought-resistant and improving the quality of its fruit. As a result of climate change, droughts are occurring more frequently and persisting for more extended periods, making it necessary to breed crops resistant to drought. While considerable variability for tolerance exists in wild cousins, little is known about the processes and essential genes influencing drought tolerance in cultivated tomato species.PMID:37939107 | DOI:10.1371/journal.pone.0281293

Cell Rep. 2023 Nov 7;42(11):113374. doi: 10.1016/j.celrep.2023.113374. Online ahead of print.ABSTRACTGlioblastoma (GBM) is the most common and aggressive primary brain malignancy. Adhesion G protein-coupled receptors (aGPCRs) have attracted interest for their potential as treatment targets. Here, we show that CD97 (ADGRE5) is the most promising aGPCR target in GBM, by virtue of its de novo expression compared to healthy brain tissue. CD97 knockdown or knockout significantly reduces the tumor initiation capacity of patient-derived GBM cultures (PDGCs) in vitro and in vivo. We find that CD97 promotes glycolytic metabolism via the mitogen-activated protein kinase (MAPK) pathway, which depends on phosphorylation of its C terminus and recruitment of β-arrestin. We also demonstrate that THY1/CD90 is a likely CD97 ligand in GBM. Lastly, we show that an anti-CD97 antibody-drug conjugate selectively kills tumor cells in vitro. Our studies identify CD97 as a regulator of tumor metabolism, elucidate mechanisms of receptor activation and signaling, and provide strong scientific rationale for developing biologics to target it therapeutically in GBM.PMID:37938973 | DOI:10.1016/j.celrep.2023.113374

Eur J Hum Genet. 2023 Nov 8. doi: 10.1038/s41431-023-01462-1. Online ahead of print.ABSTRACTCOVID-19, the disease caused by SARS-CoV-2, has caused significant morbidity and mortality worldwide. The betacoronavirus continues to evolve with global health implications as we race to learn more to curb its transmission, evolution, and sequelae. The focus of this review, the second of a three-part series, is on the biological effects of the SARS-CoV-2 virus on post-acute disease in the context of tissue and organ adaptations and damage. We highlight the current knowledge and describe how virological, animal, and clinical studies have shed light on the mechanisms driving the varied clinical diagnoses and observations of COVID-19 patients. Moreover, we describe how investigations into SARS-CoV-2 effects have informed the understanding of viral pathogenesis and provide innovative pathways for future research on the mechanisms of viral diseases.PMID:37938797 | DOI:10.1038/s41431-023-01462-1

ISME Commun. 2022 Mar 30;2(1):30. doi: 10.1038/s43705-022-00114-7.ABSTRACTThe sea anemone, Exaiptasia diaphana, is a model of coral-dinoflagellate (Symbiodiniaceae) symbiosis. However, little is known of its potential to form symbiosis with Cladocopium-a key Indo-Pacific algal symbiont of scleractinian corals, nor the host nutritional consequences of such an association. Aposymbiotic anemones were inoculated with homologous algal symbionts, Breviolum minutum, and seven heterologous strains of Cladocopium C1acro (wild-type and heat-evolved) under ambient conditions. Despite lower initial algal cell density, Cladocopium C1acro-anemeones achieved similar cell densities as B. minutum-anemones by week 77. Wild-type and heat-evolved Cladocopium C1acro showed similar colonization patterns. Targeted LC-MS-based metabolomics revealed that almost all significantly different metabolites in the host and Symbiodiniaceae fractions were due to differences between Cladocopium C1acro and B. minutum, with little difference between heat-evolved and wild-type Cladocopium C1acro at week 9. The algal fraction of Cladocopium C1acro-anemones was enriched in metabolites related to nitrogen storage, while the host fraction of B. minutum-anemones was enriched in sugar-related metabolites. Compared to B. minutum, Cladocopium C1acro is likely slightly less nutritionally beneficial to the host under ambient conditions, but more capable of maintaining its own growth when host nitrogen supply is limited. Our findings demonstrate the value of E. diaphana to study experimentally evolved Cladocopium.PMID:37938648 | DOI:10.1038/s43705-022-00114-7

Naunyn Schmiedebergs Arch Pharmacol. 2023 Nov 8. doi: 10.1007/s00210-023-02785-y. Online ahead of print.ABSTRACTCurcumin, a polyphenolic compound derived from the turmeric plant (Curcuma longa), has been extensively studied for its anti-inflammatory and anti-proliferative properties. The safety and efficacy of curcumin have been thoroughly validated. Nevertheless, the underlying mechanism for treating osteoarthritis remains ambiguous. This study aims to reveal the potential mechanism of curcumin in treating osteoarthritis by using metabolomics and transcriptomics. Firstly, we validated the effect of curcumin on inflammatory factors in human articular chondrocytes. Secondly, we explored the cellular metabolism mechanism of curcumin against osteoarthritis using cell metabolomics. Thirdly, we assessed the differences in gene expression of human articular chondrocytes through transcriptomics. Lastly, to evaluate the essential targets and elucidate the potential mechanism underlying the therapeutic effects of curcumin in osteoarthritis, we conducted a screening of the proteins within the shared pathway of metabolomics and transcriptomics. Our results demonstrated that curcumin significantly decreased the levels of inflammatory markers, such as IL-β, IL-6, and TNF-α, in human articular chondrocytes. Cell metabolomics identified 106 differential metabolites, including beta-aminopropionitrile, 3-amino-2-piperidone, pyrrole-2-carboxaldehyde, and various other components. The transcriptomic analysis yielded 1050 differential mRNAs. Enrichment analysis showed that the differential metabolites and mRNAs were significantly enriched in seven pathways, including glycine, serine, and threonine metabolism; pentose and glucuronate interconversions; glycerolipid metabolism; histidine metabolism; mucin-type o-glycan biosynthesis; inositol phosphate metabolism; and cysteine and methionine metabolism. A total of 23 key targets were identified to be involved in these pathways. We speculate that curcumin may alleviate osteoarthritis by targeting key proteins involved in glycine, serine, and threonine metabolism; inhibiting pyruvate production; and modulating glycolysis.PMID:37938371 | DOI:10.1007/s00210-023-02785-y

J Plant Res. 2023 Nov 8. doi: 10.1007/s10265-023-01500-5. Online ahead of print.ABSTRACTPrunus mume is an important medicinal plant with ornamental and edible value. Its flowers contain phenylpropanoids, flavonoids and other active components, that have important medicinal and edible value, yet their molecular regulatory mechanisms in P. mume remain unclear. In this study, the content of total flavonoid and total phenylpropanoid of P. mume at different developmental periods was measured first, and the results showed that the content of total flavonoid and total phenylpropanoid gradually decreased in three developmental periods. Then, an integrated analysis of transcriptome and metabolome was conducted on three developmental periods of P. mume to investigate the law of synthetic accumulation for P. mume metabolites, and the key enzyme genes for the biosynthesis of phenylpropanoids and flavonoids were screened out according to the differentially expressed genes (DEGs). A total of 14,332 DEGs and 38 differentially accumulate metabolites (DAMs) were obtained by transcriptomics and metabolomics analysis. The key enzyme genes and metabolites in the bud (HL) were significantly different from those in the half-opening (BK) and full-opening (QK) periods. In the phenylpropanoid and flavonoid biosynthesis pathway, the ion abundance of chlorogenic acid, naringenin, kaempferol, isoquercitrin, rutin and other metabolites decreased with the development of flowers, while the ion abundance of cinnamic acid increased. Key enzyme genes such as HCT, CCR, COMT, CHS, F3H, and FLS positively regulate the downstream metabolites, while PAL, C4H, and 4CL negatively regulate the downstream metabolites. Moreover, the key genes FLS (CL4312-2, CL4312-3, CL4312-4, CL4312-5, CL4312-6) regulating the synthesis of flavonols are highly expressed in bud samples. The dynamic changes of these metabolites were validated by determining the content of 14 phenylpropanoids and flavonoids in P. mume at different developmental periods, and the transcription expression levels of these genes were validated by real-time PCR. Our study provides new insights into the molecular mechanism of phenylpropanoid and flavonoid accumulation in P. mume.PMID:37938365 | DOI:10.1007/s10265-023-01500-5

ISME Commun. 2022 Oct 17;2(1):101. doi: 10.1038/s43705-022-00184-7.ABSTRACTBenthic organisms are the architectural framework supporting coral reef ecosystems, but their community composition has recently shifted on many reefs. Little is known about the metabolites released from these benthic organisms and how compositional shifts may influence other reef life, including prolific microorganisms. To investigate the metabolite composition of benthic exudates and their ecological significance for reef microbial communities, we harvested exudates from six species of Caribbean benthic organisms including stony corals, octocorals, and an invasive encrusting alga, and subjected these exudates to untargeted and targeted metabolomics approaches using liquid chromatography-mass spectrometry. Incubations with reef seawater microorganisms were conducted to monitor changes in microbial abundances and community composition using 16 S rRNA gene sequencing in relation to exudate source and three specific metabolites. Exudates were enriched in amino acids, nucleosides, vitamins, and indole-based metabolites, showing that benthic organisms contribute labile organic matter to reefs. Furthermore, exudate compositions were species-specific, and riboflavin and pantothenic acid emerged as significant coral-produced metabolites, while caffeine emerged as a significant invasive algal-produced metabolite. Microbial abundances and individual microbial taxa responded differently to exudates from stony corals and octocorals, demonstrating that exudate mixtures released from different coral species select for specific bacteria. In contrast, microbial communities did not respond to individual additions of riboflavin, pantothenic acid, or caffeine. This work indicates that recent shifts in benthic organisms alter exudate composition and likely impact microbial communities on coral reefs.PMID:37938276 | DOI:10.1038/s43705-022-00184-7

ISME Commun. 2022 Oct 1;2(1):94. doi: 10.1038/s43705-022-00169-6.ABSTRACTThe fate of oceanic carbon and nutrients depends on interactions between viruses, prokaryotes, and unicellular eukaryotes (protists) in a highly interconnected planktonic food web. To date, few controlled mechanistic studies of these interactions exist, and where they do, they are largely pairwise, focusing either on viral infection (i.e., virocells) or protist predation. Here we studied population-level responses of Synechococcus cyanobacterial virocells (i.e., cyanovirocells) to the protist Oxyrrhis marina using transcriptomics, endo- and exo-metabolomics, photosynthetic efficiency measurements, and microscopy. Protist presence had no measurable impact on Synechococcus transcripts or endometabolites. The cyanovirocells alone had a smaller intracellular transcriptional and metabolic response than cyanovirocells co-cultured with protists, displaying known patterns of virus-mediated metabolic reprogramming while releasing diverse exometabolites during infection. When protists were added, several exometabolites disappeared, suggesting microbial consumption. In addition, the intracellular cyanovirocell impact was largest, with 4.5- and 10-fold more host transcripts and endometabolites, respectively, responding to protists, especially those involved in resource and energy production. Physiologically, photosynthetic efficiency also increased, and together with the transcriptomics and metabolomics findings suggest that cyanovirocell metabolic demand is highest when protists are present. These data illustrate cyanovirocell responses to protist presence that are not yet considered when linking microbial physiology to global-scale biogeochemical processes.PMID:37938263 | DOI:10.1038/s43705-022-00169-6

Sci Rep. 2023 Nov 8;13(1):19382. doi: 10.1038/s41598-023-45997-1.ABSTRACTMany mammals rely on volatile organic chemical compounds (VOCs) produced by bacteria for their communication and behavior, though little is known about the exact molecular mechanisms or bacterial species that are responsible. We used metagenomic sequencing, mass-spectrometry based metabolomics, and culturing to profile the microbial and volatile chemical constituents of anal gland secretions in twenty-three domestic cats (Felis catus), in attempts to identify organisms potentially involved in host odor production. We found that the anal gland microbiome was dominated by bacteria in the genera Corynebacterium, Bacteroides, Proteus, Lactobacillus, and Streptococcus, and showed striking variation among individual cats. Microbiome profiles also varied with host age and obesity. Metabolites such as fatty-acids, ketones, aldehydes and alcohols were detected in glandular secretions. Overall, microbiome and metabolome profiles were modestly correlated (r = 0.17), indicating that a relationship exists between the bacteria in the gland and the metabolites produced in the gland. Functional analyses revealed the presence of genes predicted to code for enzymes involved in VOC metabolism such as dehydrogenases, reductases, and decarboxylases. From metagenomic data, we generated 85 high-quality metagenome assembled genomes (MAGs). Of importance were four MAGs classified as Corynebacterium frankenforstense, Proteus mirabilis, Lactobacillus johnsonii, and Bacteroides fragilis. They represent strong candidates for further investigation of the mechanisms of volatile synthesis and scent production in the mammalian anal gland.PMID:37938241 | DOI:10.1038/s41598-023-45997-1

Commun Biol. 2023 Nov 8;6(1):1133. doi: 10.1038/s42003-023-05492-9.ABSTRACTPrevious reports have provided evidence that insufficient or excessive maternal folic acid (FA) intake during pregnancy can alter neurodevelopment of the offspring by modulating prenatal neurogenesis. Furthermore, our earlier work in a mouse model confirmed long-term structural changes at the cellular level of either deficient or excessive FA supply by comparably reducing dendritic arborization of cortical projection neurons. Here, we report that excessive amounts of FA decrease arborization of deep layer projection neurons, but not upper layer neurons and that reduced complexity of deep layer neurons is not observed when folic acid is replaced by folinic acid, a stable reduced form of folate. In addition, deficiency of B12, a vitamin that critically regulates folate metabolism, causes even more marked decreases in neuronal arborization in both deep and upper layer neurons and particularly in combination with FA excess. Furthermore, both FA excess and B12 deficiency affect synaptic density and morphology. Our findings point to neurodevelopmental risks associated with insufficient amounts of prenatal B12, particularly in association with high levels of FA intake, suggesting that the neurodevelopmental program is sensitive to an imbalance in the status of these interacting micronutrients.PMID:37938221 | DOI:10.1038/s42003-023-05492-9