PubMed

mSystems. 2024 Mar 12:e0006424. doi: 10.1128/msystems.00064-24. Online ahead of print.ABSTRACTDuring prolonged resource limitation, bacterial cells can persist in metabolically active states of non-growth. These maintenance periods, such as those experienced in stationary phase, can include upregulation of secondary metabolism and release of exometabolites into the local environment. As resource limitation is common in many environmental microbial habitats, we hypothesized that neighboring bacterial populations employ exometabolites to compete or cooperate during maintenance and that these exometabolite-facilitated interactions can drive community outcomes. Here, we evaluated the consequences of exometabolite interactions over the stationary phase among three environmental strains: Burkholderia thailandensis E264, Chromobacterium subtsugae ATCC 31532, and Pseudomonas syringae pv. tomato DC3000. We assembled them into synthetic communities that only permitted chemical interactions. We compared the responses (transcripts) and outputs (exometabolites) of each member with and without neighbors. We found that transcriptional dynamics were changed with different neighbors and that some of these changes were coordinated between members. The dominant competitor B. thailandensis consistently upregulated biosynthetic gene clusters to produce bioactive exometabolites for both exploitative and interference competition. These results demonstrate that competition strategies during maintenance can contribute to community-level outcomes. It also suggests that the traditional concept of defining competitiveness by growth outcomes may be narrow and that maintenance competition could be an additional or alternative measure.IMPORTANCE: Free-living microbial populations often persist and engage in environments that offer few or inconsistently available resources. Thus, it is important to investigate microbial interactions in this common and ecologically relevant condition of non-growth. This work investigates the consequences of resource limitation for community metabolic output and for population interactions in simple synthetic bacterial communities. Despite non-growth, we observed active, exometabolite-mediated competition among the bacterial populations. Many of these interactions and produced exometabolites were dependent on the community composition but we also observed that one dominant competitor consistently produced interfering exometabolites regardless. These results are important for predicting and understanding microbial interactions in resource-limited environments.PMID:38470039 | DOI:10.1128/msystems.00064-24

Adv Healthc Mater. 2024 Mar 12:e2303995. doi: 10.1002/adhm.202303995. Online ahead of print.ABSTRACTRheumatoid arthritis (RA) causes inflammatory and metabolic imbalances in tissue, which then exacerbates inflammation in affected joints. Therefore, restoring tissue homeostasis is necessary for the remission of RA symptoms. In fact, the changes in immunological and metabolic tissue homeostasis at different stages of the disease is not well understood. Herein, the changes in the immunological metabolic profiles in different stages of RA namely, early, intermediate, and late stage was examined. Moreover, the efficacy of the microparticle inverse-vaccine, paKG(PFK15+bc2) to restore immunological and metabolic tissue homeostasis at different stages of the disease was also investigated. Analysis of the immune cell profiles revealed that there was a significant decrease in the activation of pro-inflammatory immune cells while a remarkable increase was seen in regulatory T-cell populations in the intermediate and late stages of RA in the inverse-vaccine treated group as compared to no treatment. Also, it was determined that glycolysis in the spleen was normalized in the late stages of CIA, which was similar to no disease tissues. Using metabolomics we identified, key metabolites UDP-glucuronic acid and L-Glutathione oxidized that were significantly altered between treatment groups, and thus might provide new druggable targets for RA. We also employed flux metabolic modeling of the metabolomics data to identify amino acid and carnitine pathways as the central pathways affected at the tissue-level in CIA as the disease progresses. Overall, this study shows that the inverse-vaccines initiate early re-establishment of homeostasis and persists through the disease span. This article is protected by copyright. All rights reserved.PMID:38469995 | DOI:10.1002/adhm.202303995

Am J Physiol Lung Cell Mol Physiol. 2024 Mar 12. doi: 10.1152/ajplung.00266.2023. Online ahead of print.ABSTRACTAcute respiratory distress syndrome (ARDS) is a fatal pulmonary disorder characterized by severe hypoxia and inflammation. Systemic and pulmonary infections are a leading cause of ARDS. The common respiratory pathogens include bacteria and virus, including Pseudomonas aeruginosa, Streptococcus aureus, Enterobacter species, coronavirus, influenza, and herpesviruses. COVID-19-associated ARDS is a new etiologic phenotype of the disease. The pathogenesis of ARDS caused by bacteria and viruses differs in host immune responses and lung mesenchymal injury. We postulate that both systemic and lung metabolomics of ARDS induced by virus may differ from those infected by other pathogens. This review aims to compare the metabolic signatures in blood and lung specimens. Both common and SARS-CoV-2-specific metabolomic signatures were comprehensively reviewed. The differences in metabolic profiles between COVID-19 and other etiology-associated ARDS may uncover new biomarkers, pathogenic mechanisms, druggable targets, and differential diagnosis.PMID:38469648 | DOI:10.1152/ajplung.00266.2023

Front Gastroenterol (Lausanne). 2023;2:1087056. doi: 10.3389/fgstr.2023.1087056. Epub 2023 Feb 15.ABSTRACTINTRODUCTION: Dietary intake of whole grains and legumes and adequate physical activity (PA) have been associated with reduced colorectal cancer (CRC) risk. A single-blinded, two-arm, randomized, placebo-controlled pilot trial was implemented to evaluate the impact of a 12-week dietary intervention of rice bran + navy bean supplementation and PA education on metabolite profiles and the gut microbiome among individuals at high risk of CRC.METHODS: Adults (n=20) were randomized 1:1 to dietary intervention or control. All participants received PA education at baseline. Sixteen study foods were prepared with either heat-stabilized rice bran + navy bean powder or Fibersol®-2 as a placebo. Intervention participants consumed 30 g rice bran + 30 g navy bean powder daily; those in the control group consumed 10 g placebo daily. Non-targeted metabolite profiling was performed by UPLC-MS/MS to evaluate plasma, urine, and stool at 0, 6, and 12 weeks. Stool was also analyzed for primary and secondary bile acids (BAs) and short chain fatty acids (SCFAs) by UPLC-MS/MS and microbial community structure via 16S amplicon sequencing. Two-way ANOVA was used to compare differences between groups for metabolites, and mixed models were used to compare differences between groups for BAs, SCFAs, and alpha and beta diversity measures of microbial community structure.RESULTS: Across biological matrices, the intervention resulted in changes to several amino acid and lipid metabolites, compared to control. There was a 2.33-fold difference in plasma (p<0.001) and a 3.33-fold difference in urine (p=0.008) for the amino acid S-methylcysteine at 12 weeks. Fold-differences to 4-methoxyphenol sulfate in plasma and urine after 6 and 12 weeks (p<0.001) was a novel result from this combined rice bran and navy bean intervention in people. A 2.98-fold difference in plasma (p=0.002) and a 17.74-fold difference in stool (p=0.026) was observed for the lipid octadecenedioylcarnitine at 12 weeks. For stool BAs, 3-oxocholic acid was increased at 12 weeks compared to control within a subset of individuals (mean difference 16.2 ug/uL, p=0.022). No significant differences were observed between groups for stool SCFAs or microbial community structure.DISCUSSION: Dietary intake of rice bran + navy beans demonstrates beneficial modulation of host and gut microbial metabolism and represents a practical and affordable means of increasing adherence to national guidelines for CRC control and prevention in a high-risk population.PMID:38469373 | PMC:PMC10927265 | DOI:10.3389/fgstr.2023.1087056

Front Immunol. 2024 Feb 26;15:1347871. doi: 10.3389/fimmu.2024.1347871. eCollection 2024.ABSTRACTThe antibody- FcγRIIIa interaction triggers key immunological responses such as antibody dependent cellular cytotoxicity (ADCC), making it highly important for therapeutic mAbs. Due to the direct glycan-glycan interaction with FcγRIIIa receptor, differences in antibody glycosylation can drastically influence the binding affinity. Understanding the differential binding of mAb glycoforms is a very important, yet challenging task due to the co-existence of multiple glycoforms in a sample. Affinity liquid chromatography (AC) and affinity capillary electrophoresis (ACE) hyphenated with mass spectrometry (MS) can provide glycoform-resolved affinity profiles of proteins based on their differences in either dissociation (AC) or equilibrium (ACE) constants. To cross-validate the affinity ranking provided by these complementary novel approaches, both techniques were benchmarked using the same FcγRIIIa constructs. Both approaches were able to assess the mAb - FcγRIIIa interaction in a glycoform selective manner and showed a clear increase in binding for fully versus hemi-fucosylated mAbs. Also, other features, such as increasing affinity with elevated galactosylation or the binding affinity for high mannose glycoforms were consistent. We further applied these approaches to assess the binding towards the F158 allotype of FcγRIIIa, which was not reported before. The FcγRIIIa F158 allotype showed a very similar profile compared to the V158 receptor with the strongest increase in binding due to afucosylation and only a slight increase in binding with additional galactosylation. Both techniques showed a decrease of the binding affinity for high mannose glycoforms for FcγRIIIa F158 compared to the V158 variant. Overall, both approaches provided very comparable results in line with orthogonal methods proving the capabilities of separation-based affinity approaches to study FcγR binding of antibody glycoforms.PMID:38469305 | PMC:PMC10925690 | DOI:10.3389/fimmu.2024.1347871

Health Sci Rep. 2024 Mar 10;7(3):e1895. doi: 10.1002/hsr2.1895. eCollection 2024 Mar.ABSTRACTBACKGROUND AND AIMS: The aim is to investigate the cause-and-effect connection between metabolites found in blood/urine and the likelihood of developing periodontal disease (PD) through the utilization of a two-sample Mendelian randomization (MR) method.METHODS: Using an inverse variance weighted (IVW) method and two additional two-sample MR models, we examined the relationship between blood/urine metabolites and PD by analyzing data from a comprehensive metabolome-based genome-wide association study and the Genome-Wide Association Studies (GWAS) of PD. To assess the consistency and dependability of the findings, diversity, cross-effects, and sensitivity analyses were conducted.RESULTS: Out of the 35 metabolites found in blood and urine, a total of eight metabolites (C-reactive protein, Potassium in urine, Urea, Cystatin C, Non-albumin protein, Creatinine, estimated Glomerular Filtration Rate, and Phosphate) displayed a possible causal connection with the risk of dental caries/PD using the inverse variance weighted (IVW) method (p < 0.05). This includes five metabolites in the blood and three in the urine. No metabolites were statistically significant in IVW MR models (p < 3.68 × 10- 4). Even after conducting sensitivity analysis with the leave-one-out method and removing the confounding instrumental variables, the impact of these factors on dental caries/PD remained significant.CONCLUSION: Based on the available evidence, it is not possible to establish a significant causal link between the 35 blood metabolites and the likelihood of developing dental caries and PD.PMID:38469110 | PMC:PMC10925816 | DOI:10.1002/hsr2.1895

Sleep Biol Rhythms. 2023 Feb 8;21(3):265-277. doi: 10.1007/s41105-023-00445-5. eCollection 2023 Jul.ABSTRACTObstructive Sleep Apnea (OSA) corresponds to episodes of complete or partial upper airway obstruction during sleep. The gold standard for diagnosing OSA is polysomnography; however, metabolomics is an innovative and highly sensitive method that seeks to identify and quantify small molecules in biological systems. Identify the metabolites most frequently associated with obstructive sleep apnea in adults. The search for articles was conducted between October 2020 and August 2021, in electronic databases, such as MEDLINE/PubMed, Scielo, Embase, and Cochrane, through the combination of descriptors: obstructive sleep apnea, metabolomic, adult. This systematic review included all cross-sectional studies published, including human patients aged 18 years or older, of both genders who underwent type I or II polysomnography and metabolomics study. The search strategy selected 3697 surveys, and 4 of them were selected to be a part of this systematic review. Based on the analyzed surveys, it was found that all of them were able to diagnose OSA, reaching a sensitivity of 75-97%, and specificity that ranged from 72 to 100%; besides differentiating patients with OSA (severe, moderate, and mild) from simple snorers with a mean sensitivity of 77.2% and specificity of 66.25%. These findings suggest that, in addition to being used as a screening and diagnostic strategy for OSA, metabolomics has the potential to be used for severity stratification and to monitor the disease's progression.PMID:38469078 | PMC:PMC10899929 | DOI:10.1007/s41105-023-00445-5

Front Microbiol. 2024 Feb 26;15:1268813. doi: 10.3389/fmicb.2024.1268813. eCollection 2024.ABSTRACTBacterial outer membrane vesicles (OMVs) contain a variety of chemical compounds and play significant roles in maintaining symbiotic relationships in a changing ocean, but little is known about their function, particularly in sponge larval development. During the growth of sponge Tedania sp., OMVs from Bacteroidetes species significantly promoted larval settlement, and Tenacibaculum mesophilum SP-7-OMVs were selected as a representative strain for further investigation. According to OMVs metabolomics, larval settlement might be connected to organic acids and derivatives. The multiomics analysis of the T. mesophilum genome, SP-7-OMVs metabolome, and larval transcriptome revealed 47 shared KEGG pathways. Among the number of candidate metabolites, arginine was chosen for its greater ability to increase the settlement rate and its role as the principal substrate for nitric oxide (NO) synthesis of sponge larvae. In summary, these results demonstrated that sponge-associated bacteria might utilize OMVs and their cargo to support host development and make up for host metabolic pathway deficiencies. This study enhances our fundamental knowledge of OMVs in interactions between metazoan hosts and microorganisms that are crucial in the coevolution of marine ecosystems and the complex marine environment.PMID:38468855 | PMC:PMC10925772 | DOI:10.3389/fmicb.2024.1268813

Food Chem X. 2024 Mar 1;22:101265. doi: 10.1016/j.fochx.2024.101265. eCollection 2024 Jun 30.ABSTRACTAdulteration in dairy products presents food safety challenges, driven by economic factors. Processing may change specific biomarkers, thus affecting their effectiveness in detection. In this study, proteomics and metabolomics approaches were to investigate the detection of bovine milk (BM) constituents adulteration in pasteurized mare milk (PMM) and mare milk powder (MMP). Several bovine proteins and metabolites were identified, with their abundances in PMM and MMP increasing upon addition of BM. Proteins like osteopontin (OPN) and serotransferrin (TF) detected adulteration down to 1 % in PMM, whereas these proteins in MMP were utilized to identify 10 % adulteration. Biotin and N6-Me-adenosine were effective in detecting adulteration in PMM as low as 10 % and 1 % respectively, while in MMP, their detection limits extend down to 0.1 %. These findings offer insights for authenticating mare milk products and underscore the influence of processing methods on biomarker levels, stressing the need to consider these effects in milk product authentication.PMID:38468636 | PMC:PMC10926301 | DOI:10.1016/j.fochx.2024.101265

Food Chem X. 2024 Mar 1;22:101264. doi: 10.1016/j.fochx.2024.101264. eCollection 2024 Jun 30.ABSTRACTWorkshop with different fermentation years plays an essential role in the yield and quality of Baijiu. In actual production, the quality of base Baijiu in newly built workshop is inferior to the older one. In this study, the microbiota of workshop environment and fermentation process from two workshops namely N (ferment 2 years) and O (ferment 20 years) and flavor compounds were studied during Xiasha round. Results showed workshop O accumulated more environmental microorganisms and fungi including P. kudriavzevii, Wickerhamomyces anomalus and Saccharomyces sp mainly came from ground. Yeasts including Pichia, Cyberlindnera, Wickerhamomyces and Candida were responsible for flavor substances formation in O while Saccharopolyspora was in N. This study for the first time explored the reasons for the brewing differences among N and O workshop from perspectives of workshop environment, microbial community and flavor substances, providing new ideas for guiding production as well as improvement of Baijiu quality.PMID:38468635 | PMC:PMC10926306 | DOI:10.1016/j.fochx.2024.101264

Clin Transl Med. 2024 Mar;14(3):e1624. doi: 10.1002/ctm2.1624.NO ABSTRACTPMID:38468504 | DOI:10.1002/ctm2.1624

Eur J Heart Fail. 2024 Mar 11. doi: 10.1002/ejhf.3192. Online ahead of print.ABSTRACTAIMS: Patients with heart failure and reduced ejection fraction (HFrEF) exhibit skeletal muscle pathology, which contributes to symptoms and decreased quality of life. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve clinical outcomes in HFrEF but their mechanism of action remains poorly understood. We aimed, therefore, to determine whether SGLT2i influence skeletal muscle pathology in patients with HFrEF.METHODS AND RESULTS: Muscle biopsies from 28 male patients with HFrEF (New York Heart association class I-III) treated with SGLT2i (>12 months) or without SGLT2i were compared. Comprehensive analyses of muscle structure (immunohistochemistry), transcriptome (RNA sequencing), and metabolome (liquid chromatography-mass spectrometry) were performed, and serum inflammatory profiling (ELISA). Experiments in mice (n = 16) treated with SGLT2i were also performed. Myofiber atrophy was ~20% less in patients taking SGLT2i (p = 0.07). Transcriptomics and follow-up measures identified a unique signature in patients taking SGLT2i related to beneficial effects on atrophy, metabolism, and inflammation. Metabolomics identified influenced tryptophan metabolism in patients taking SGLT2i: kynurenic acid was 24% higher and kynurenine was 32% lower (p < 0.001). Serum profiling identified that SGLT2i treatment was associated with lower (p < 0.05) pro-inflammatory cytokines by 26-64% alongside downstream muscle interleukin (IL)-6-JAK/STAT3 signalling (p = 008 and 0.09). Serum IL-6 and muscle kynurenine were correlated (R = 0.65; p < 0.05). Muscle pathology was lower in mice treated with SGLT2i indicative of a conserved mammalian response to treatment.CONCLUSIONS: Treatment with SGLT2i influenced skeletal muscle pathology in patients with HFrEF and was associated with anti-atrophic, anti-inflammatory, and pro-metabolic effects. These changes may be regulated via IL-6-kynurenine signalling. Together, clinical improvements following SGLT2i treatment in patients with HFrEF may be partly explained by their positive effects on skeletal muscle pathology.PMID:38468429 | DOI:10.1002/ejhf.3192

Genome Biol. 2024 Mar 11;25(1):66. doi: 10.1186/s13059-024-03208-8.ABSTRACTBACKGROUND: Oncometabolites, often generated as a result of a gene mutation, show pro-oncogenic function when abnormally accumulated in cancer cells. Identification of such mutation-associated metabolites will facilitate developing treatment strategies for cancers, but is challenging due to the large number of metabolites in a cell and the presence of multiple genes associated with cancer development.RESULTS: Here we report the development of a computational workflow that predicts metabolite-gene-pathway sets. Metabolite-gene-pathway sets present metabolites and metabolic pathways significantly associated with specific somatic mutations in cancers. The computational workflow uses both cancer patient-specific genome-scale metabolic models (GEMs) and mutation data to generate metabolite-gene-pathway sets. A GEM is a computational model that predicts reaction fluxes at a genome scale and can be constructed in a cell-specific manner by using omics data. The computational workflow is first validated by comparing the resulting metabolite-gene pairs with multi-omics data (i.e., mutation data, RNA-seq data, and metabolome data) from acute myeloid leukemia and renal cell carcinoma samples collected in this study. The computational workflow is further validated by evaluating the metabolite-gene-pathway sets predicted for 18 cancer types, by using RNA-seq data publicly available, in comparison with the reported studies. Therapeutic potential of the resulting metabolite-gene-pathway sets is also discussed.CONCLUSIONS: Validation of the metabolite-gene-pathway set-predicting computational workflow indicates that a decent number of metabolites and metabolic pathways appear to be significantly associated with specific somatic mutations. The computational workflow and the resulting metabolite-gene-pathway sets will help identify novel oncometabolites and also suggest cancer treatment strategies.PMID:38468344 | DOI:10.1186/s13059-024-03208-8

Microbiome. 2024 Mar 12;12(1):50. doi: 10.1186/s40168-023-01746-0.ABSTRACTBACKGROUND: Antibiotics notoriously perturb the gut microbiota. We treated healthy volunteers either with cefotaxime or ceftriaxone for 3 days, and collected in each subject 12 faecal samples up to day 90. Using untargeted and targeted phenotypic and genotypic approaches, we studied the changes in the bacterial, phage and fungal components of the microbiota as well as the metabolome and the β-lactamase activity of the stools. This allowed assessing their degrees of perturbation and resilience.RESULTS: While only two subjects had detectable concentrations of antibiotics in their faeces, suggesting important antibiotic degradation in the gut, the intravenous treatment perturbed very significantly the bacterial and phage microbiota, as well as the composition of the metabolome. In contrast, treatment impact was relatively low on the fungal microbiota. At the end of the surveillance period, we found evidence of resilience across the gut system since most components returned to a state like the initial one, even if the structure of the bacterial microbiota changed and the dynamics of the different components over time were rarely correlated. The observed richness of the antibiotic resistance genes repertoire was significantly reduced up to day 30, while a significant increase in the relative abundance of β-lactamase encoding genes was observed up to day 10, consistent with a concomitant increase in the β-lactamase activity of the microbiota. The level of β-lactamase activity at baseline was positively associated with the resilience of the metabolome content of the stools.CONCLUSIONS: In healthy adults, antibiotics perturb many components of the microbiota, which return close to the baseline state within 30 days. These data suggest an important role of endogenous β-lactamase-producing anaerobes in protecting the functions of the microbiota by de-activating the antibiotics reaching the colon. Video Abstract.PMID:38468305 | DOI:10.1186/s40168-023-01746-0

Probiotics Antimicrob Proteins. 2024 Mar 12. doi: 10.1007/s12602-024-10232-4. Online ahead of print.ABSTRACTDiarrhea, a common gastrointestinal symptom in health problems, is highly associated with gut dysbiosis. The purpose of this study is to demonstrate the effect of multistrain probiotics (Sensi-Biome) on diarrhea from the perspective of the microbiome-neuron axis. Sensi-Biome (Lactiplantibacillus plantarum, Bifidobacterium animalis subsp. lactis, Lactobacillus acidophilus, Streptococcus thermophilus, Bifidobacterium bifidum, and Lactococcus lactis) was administered in a 4% acetic acid-induced diarrhea rat model at concentrations of 1 × 108 (G1), 1 × 109 (G2), and 1 × 1010 CFU/0.5 mL (G3). Diarrhea-related parameters, inflammation-related cytokines, and stool microbiota analysis by 16S rRNA were evaluated. A targeted and untargeted metabolomics approach was used to analyze the cecum samples using liquid chromatography and orbitrap mass spectrometry. The stool moisture content (p < 0.001), intestinal movement rate (p < 0.05), and pH (p < 0.05) were significantly recovered in G3. Serotonin levels were decreased in the multistrain probiotics groups. The inflammatory cytokines, serotonin, and tryptophan hydroxylase expression were improved in the Sensi-Biome groups. At the phylum level, Sensi-Biome showed the highest relative abundance of Firmicutes. Short-chain fatty acids including butyrate, iso-butyrate, propionate, and iso-valeric acid were significantly modified in the Sensi-Biome groups. Equol and oleamide were significantly improved in the multistrain probiotics groups. In conclusion, Sensi-Biome effectively controls diarrhea by modulating metabolites and the serotonin pathway.PMID:38467925 | DOI:10.1007/s12602-024-10232-4

Mol Syst Biol. 2024 Mar 11. doi: 10.1038/s44320-024-00027-8. Online ahead of print.ABSTRACTMicrobial biochemistry is central to the pathophysiology of inflammatory bowel diseases (IBD). Improved knowledge of microbial metabolites and their immunomodulatory roles is thus necessary for diagnosis and management. Here, we systematically analyzed the chemical, ecological, and epidemiological properties of ~82k metabolic features in 546 Integrative Human Microbiome Project (iHMP/HMP2) metabolomes, using a newly developed methodology for bioactive compound prioritization from microbial communities. This suggested >1000 metabolic features as potentially bioactive in IBD and associated ~43% of prevalent, unannotated features with at least one well-characterized metabolite, thereby providing initial information for further characterization of a significant portion of the fecal metabolome. Prioritized features included known IBD-linked chemical families such as bile acids and short-chain fatty acids, and less-explored bilirubin, polyamine, and vitamin derivatives, and other microbial products. One of these, nicotinamide riboside, reduced colitis scores in DSS-treated mice. The method, MACARRoN, is generalizable with the potential to improve microbial community characterization and provide therapeutic candidates.PMID:38467837 | DOI:10.1038/s44320-024-00027-8

Pediatr Res. 2024 Mar 11. doi: 10.1038/s41390-024-03111-9. Online ahead of print.ABSTRACTBACKGROUND: Despite advancements in neonatal care, germinal matrix-intraventricular hemorrhage impacts 20% of very preterm infants, exacerbating their neurological prognosis. Understanding its complex, multifactorial pathophysiology and rapid onset remains challenging. This study aims to link specific cord blood biomolecules at birth with post-natal germinal matrix-intraventricular hemorrhage onset.METHODS: A monocentric, prospective case-control study was conducted at Rouen University Hospital from 2015 to 2020. Premature newborns ( < 30 gestational age) were included and cord blood was sampled in the delivery room. A retrospective matching procedure was held in 2021 to select samples for proteomic and metabolomic analysis of 370 biomolecules.RESULTS: 26 patients with germinal matrix-intraventricular hemorrhage cases and 60 controls were included. Clinical differences were minimal, except for higher invasive ventilation rates in the germinal matrix-intraventricular hemorrhage group. Germinal matrix-intraventricular hemorrhage newborns exhibited lower phosphatidylcholine levels and elevated levels of four proteins: BOC cell adhesion-associated protein, placental growth factor, Leukocyte-associated immunoglobulin-like receptor 2, and tumor necrosis factor-related apoptosis-inducing ligand receptor 2.CONCLUSION: This study identifies biomolecules that may be linked to subsequent germinal matrix-intraventricular hemorrhage, suggesting heightened vascular disruption risk as an independent factor. These results need further validation but could serve as early germinal matrix-intraventricular hemorrhage risk biomarkers for future evaluations.IMPACT: Decrease in certain phosphatidylcholines and increase in four proteins in cord blood at birth may be linked to subsequent germinal matrix-intraventricular hemorrhage in premature newborns. The four proteins are BOC cell adhesion-associated protein, placental growth factor, leukocyte-associated immunoglobulin-like receptor 2, and TNF-related apoptosis-inducing ligand receptor 2. This biological imprint could point toward higher vascular disruption risk as an independent risk factor for this complication and with further validations, could be used for better stratification of premature newborns at birth.PMID:38467704 | DOI:10.1038/s41390-024-03111-9

Sci Rep. 2024 Mar 11;14(1):5865. doi: 10.1038/s41598-024-55920-x.ABSTRACTThe present study assessed the ability of Trichoderma to combat F. sporotrichioides, focusing on their antagonistic properties. Tests showed that Trichoderma effectively inhibited F. sporotrichioides mycelial growth, particularly with T. atroviride strains. In co-cultures on rice grains, Trichoderma almost completely reduced the biosynthesis of T-2 and HT-2 toxins by Fusarium. T-2 toxin-α-glucoside (T-2-3α-G), HT-2 toxin-α-glucoside (HT-2-3α-G), and HT-2 toxin-β-glucoside (HT-2-3β-G) were observed in the common culture medium, while these substances were not present in the control medium. The study also revealed unique metabolites and varying metabolomic profiles in joint cultures of Trichoderma and Fusarium, suggesting complex interactions. This research offers insights into the processes of biocontrol by Trichoderma, highlighting its potential as a sustainable solution for managing cereal plant pathogens and ensuring food safety.PMID:38467671 | DOI:10.1038/s41598-024-55920-x

Zhongguo Zhen Jiu. 2024 Mar 12;44(3):360-366. doi: 10.13703/j.0255-2930.20230520-k0001.ABSTRACTThe literature regarding the action mechanism of acupuncture for migraine published from 2013 to 2023 was searched in China National Knowledge Infrastructure (CNKI), Wanfang, VIP, Chinese Science and Technology Periodical Database, PubMed, Medline, and Cochrane Library. The pathogenesis of migraine and potential mechanisms of acupuncture treatment were summarized from the aspects of trigeminovascular system (TGVS), metabolic-related mechanisms, genetic factors, and alterations in brain structure and function. The results revealed that current research on the mechanisms of acupuncture for migraine predominantly centered around the TGVS, with studies confirming the specific regulatory effects of acupuncture on trigeminal system-related components, such as cortical spreading depression (CSD), astrocytes, and neurogenic kinin. While metabolic-related mechanisms and genetic factors are gaining attention, further in-depth exploration is needed to fully understand their roles in the mechanism of acupuncture for migraine. The study of brain structure and function in migraine has advanced, albeit with some controversies. Future research should prioritize larger sample sizes and standardized study designs to delve deeper into the mechanisms of acupuncture in treating migraine.PMID:38467514 | DOI:10.13703/j.0255-2930.20230520-k0001

J Ethnopharmacol. 2024 Mar 9:118019. doi: 10.1016/j.jep.2024.118019. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Clinopodium chinense Kuntze (CC) and Clinopodium polycephalum (Vaniot) C. Y. Wu & S. J. Hsuan (CP) are both included in the Pharmacopoeia of the People's Republic of China (edition 2020) as the legitimate source of "Duan Xue Liu" (DXL), which is a crucial traditional Chinese medicine used as a clinical remedy for bleeding diseases. However, the differences in plant endogenous metabolites and bioactivities between CC and CP are still unclear.AIM OF THE STUDY: This study aims to provide a scientific basis to investigate the differences between CC and CP ensuring the efficient and safe use of DXL.MATERIALS AND METHODS: A multidimensional strategy including plant metabolomics, digital reference standard (DRS) analyzer, and biological activities assay was creatively constructed for the characterization, distinction, and quality control of CC and CP.RESULTS: There were apparent differences in the metabolites between CC and CP. 7 compounds contributing to the differences were successfully identified. On that basis, linear calibration using two reference substances (LCTRS) methods was proved as a more accurate and specific quality analysis method for CC and CP. In addition, bioactivity assays showed that both CC and CP exhibited obvious hemostatic activity, while CC showed greater potential to resist inflammation and free radicals.CONCLUSION: In summary, it was the first time to investigate the chemical constituents and bioactivities differences between CC and CP with the help of plant metabolomics, DRS study, and biological activity assays. These two plants were significantly separated in the integrated analysis, suggesting that we should pay attention to the distinction to prevent unexpected risks caused by medicinal materials.PMID:38467319 | DOI:10.1016/j.jep.2024.118019