PubMed

Nat Commun. 2024 Jul 3;15(1):5578. doi: 10.1038/s41467-024-49991-7.ABSTRACTDiatoms often outnumber other eukaryotic algae in the oceans, especially in coastal environments characterized by frequent fluctuations in light intensity. The identities and operational mechanisms of regulatory factors governing diatom acclimation to high light stress remain largely elusive. Here, we identified the AUREO1c protein from the coastal diatom Phaeodactylum tricornutum as a crucial regulator of non-photochemical quenching (NPQ), a photoprotective mechanism that dissipates excess energy as heat. AUREO1c detects light stress using a light-oxygen-voltage (LOV) domain and directly activates the expression of target genes, including LI818 genes that encode NPQ effector proteins, via its bZIP DNA-binding domain. In comparison to a kinase-mediated pathway reported in the freshwater green alga Chlamydomonas reinhardtii, the AUREO1c pathway exhibits a faster response and enables accumulation of LI818 transcript and protein levels to comparable degrees between continuous high-light and fluctuating-light treatments. We propose that the AUREO1c-LI818 pathway contributes to the resilience of diatoms under dynamic light conditions.PMID:38956103 | DOI:10.1038/s41467-024-49991-7

Metabolomics. 2024 Jul 2;20(4):70. doi: 10.1007/s11306-024-02129-8.ABSTRACTINTRODUCTION: Congenital heart disease (CHD) is the most common congenital anomaly, representing a significant global disease burden. Limitations exist in our understanding of aetiology, diagnostic methodology and screening, with metabolomics offering promise in addressing these.OBJECTIVE: To evaluate maternal metabolomics and lipidomics in prediction and risk factor identification for childhood CHD.METHODS: We performed an observational study in mothers of children with CHD following pregnancy, using untargeted plasma metabolomics and lipidomics by ultrahigh performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS). 190 cases (157 mothers of children with structural CHD (sCHD); 33 mothers of children with genetic CHD (gCHD)) from the children OMACp cohort and 162 controls from the ALSPAC cohort were analysed. CHD diagnoses were stratified by severity and clinical classifications. Univariate, exploratory and supervised chemometric methods were used to identify metabolites and lipids distinguishing cases and controls, alongside predictive modelling.RESULTS: 499 metabolites and lipids were annotated and used to build PLS-DA and SO-CovSel-LDA predictive models to accurately distinguish sCHD and control groups. The best performing model had an sCHD test set mean accuracy of 94.74% (sCHD test group sensitivity 93.33%; specificity 96.00%) utilising only 11 analytes. Similar test performances were seen for gCHD. Across best performing models, 37 analytes contributed to performance including amino acids, lipids, and nucleotides.CONCLUSIONS: Here, maternal metabolomic and lipidomic analysis has facilitated the development of sensitive risk prediction models classifying mothers of children with CHD. Metabolites and lipids identified offer promise for maternal risk factor profiling, and understanding of CHD pathogenesis in the future.PMID:38955892 | DOI:10.1007/s11306-024-02129-8

Biochem Genet. 2024 Jul 2. doi: 10.1007/s10528-024-10869-4. Online ahead of print.ABSTRACTThe advent of the new coronavirus, leading to the SARS-CoV-2 pandemic, has presented a substantial worldwide health hazard since its inception in the latter part of 2019. The severity of the current pandemic is exacerbated by the occurrence of re-infection or co-infection with SARS-CoV-2. Hence, comprehending the molecular process underlying the pathophysiology of sepsis and discerning possible molecular targets for therapeutic intervention holds significant importance. For the first time, 31 metabolites were tentatively identified by GC-MS analysis from Alpinia malaccensis. On the other hand, five phenolic compounds were identified and quantified from the plant in HPLC-DAD analysis, including (-) epicatechin, rutin hydrate, rosmarinic acid, quercetin, and kaempferol. Nine GC-MS and five HPLC-identified metabolites had shown interactions with 45 and 30 COVID-19-associated human proteins, respectively. Among the proteins, PARP1, FN1, PRKCA, EGFR, ALDH2, AKR1C3, AHR, and IKBKB have been found as potential therapeutic targets to mitigate SARS-CoV-2 infection. KEGG pathway analysis also showed a strong association of FN1, EGFR, and IKBKB genes with SARS-CoV-2 viral replication and cytokine overexpression due to viral infection. Protein-protein interaction (PPI) analysis also showed that TP53, MMP9, FN1, EGFR, and NOS2 proteins are highly related to the genes involved in COVID-19 comorbidity. These proteins showed interaction with the plant phytoconstituents as well. As the study offers a robust network-based procedure for identifying biomolecules relevant to COVID-19 disease, A. malaccensis could be a good source of effective therapeutic agents against COVID-19 and related viral diseases.PMID:38955878 | DOI:10.1007/s10528-024-10869-4

Zhonghua Yu Fang Yi Xue Za Zhi. 2024 Jun 6;58(6):778-790. doi: 10.3760/cma.j.cn112150-20240124-00083.ABSTRACTObjective: To investigate the effects of subcutaneous immunotherapy (SCIT) on patients' immune markers and metabolic levels in the early stage of allergen treatment, and to gain insight into the role of SCIT in regulating immune responses and metabolic levels, so as to provide reference data for the further discovery of potential biomarkers. Methods: A longitudinal study was used to include 40 subjects who underwent SCIT with dust mite allergens in the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University between November 2017 and February 2022, including 20 subjects each of single mite subcutaneous immunotherapy (SM-SCIT) and double mite subcutaneous immunotherapy (DM-SCIT). In this study, levels of dust mite allergen-specific antibodies and polyunsaturated fatty acid metabolism were measured before and 12 months after treatment, while pulmonary function tests were performed. The therapeutic effects of the patients were followed up by visual analogue scale (VAS), asthma control test (ACT) and total medication scores (TMS). The results were statistically analyzed using t-test and Mann-Whitney U-test. Results: After 12 months of treatment with SCIT, both groups showed a significant decrease in total VAS score (SM-SCIT:Z=-2.298, P<0.05; DM-SCIT:Z=-3.411, P<0.001); total ACT score (SM-SCIT:Z=-2.054, P<0.05; DM-SCIT:Z=-2.014, P<0.05) and total medication scores (SM-SCIT:Z=-3.799, P<0.000 1; DM-SCIT:Z=-3.474, P<0.001) were significantly higher, in addition to significantly higher MMEF75/25 values in the DM-SCIT group (t=-2.253, P<0.05). There was no significant change in sIgE in the SM-SCIT group (P>0.05), and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 2, and p 21 fractions were significantly elevated (Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, and -3.285, respectively, all P<0.05); The sIgE of Der p 2, f 2, p 7 and p 23 fractions(Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, -3.285, all P<0.05) and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 1, f 2, p 10, p 21 and p 23 fractions (Z=-3.808, -3.845, -3.061, -2.688, -2.464, -3.211, -2.371, -2.091, -2.427, all P<0.05) of the DM-SCIT group were significantly elevated. Metabolomics analysis showed that arachidonic acid, docosahexaenoic acid, docosapentaenoic acid, eicosapentaenoic acid, 5, 9, 12-octadecatrienoic acid, 5(S)-hydroxylated eicosatetraenoic acid, and dihomo-gamma-linolenic acid were significantly elevated at the beginning of the treatment period after SM-SCIT treatment (Z of -2.191, -2.497, -1.988, -2.090, -2.19, -2.803, -2.073, all P<0.05); 5(S)-hydroxylated eicosatetraenoic acid showed elevated and alpha-linolenic acid, eicosadienoic acid, and eicosapentaenoic acid were significantly decreased in the DM-SCIT group after treatment (Z=-1.988, -2.090, -2.497, -1.988, respectively, all P<0.05). Correlation analysis showed that arachidonic acid was significantly negatively correlated with changes in dust mite-specific IgG4 (r=-0.499, P<0.05), and that alpha-linolenic acid, 5, 9, 12-octadecatrienoic acid, and eicosapentaenoic acid were positively correlated with the ΔsIgG4 of the dust mite der p 2 (r=0.451, 0.420, 0.474, respectively; all P<0.05). Conclusion: Significant changes in allergen-specific antibody levels and polyunsaturated fatty acid metabolism levels occur during SCIT, and the two may interact and influence each other.PMID:38955724 | DOI:10.3760/cma.j.cn112150-20240124-00083

Int J Surg. 2024 Jul 2. doi: 10.1097/JS9.0000000000001897. Online ahead of print.ABSTRACTBACKGROUND: Tibial cortex transverse transport (TTT) surgery has become an ideal treatment for patients with type 2 severe diabetic foot ulcerations (DFUs) while conventional treatments are ineffective. Based on our clinical practice experience, the protective immune response from TTT surgery may play a role against infections to promote wound healing in patients with DFUs. Therefore, this research aimed to systematically study the specific clinical efficacy and the mechanism of TTT surgery.MATERIALS AND METHODS: Between June 2022 and September 2023, 68 patients with type 2 severe DFUs were enrolled and therapized by TTT surgery in this cross-sectional and experimental study. Major clinical outcomes including limb salvage rate and antibiotics usage rate were investigated. Ten clinical characteristics and laboratory features of glucose metabolism and kidney function were statistically analyzed. Blood samples from 6 key time points of TTT surgery were collected for label-free proteomics and clinical immune biomarker analysis. Besides, tissue samples from 3 key time points were for spatially resolved metabolomics and transcriptomics analysis, as well as applied to validate the key TTT-regulated molecules by RT-qPCR.RESULTS: Notably, 64.7% of patients did not use antibiotics during the entire TTT surgery. TTT surgery can achieve a high limb salvage rate of 92.6% in patients with unilateral or bilateral DFUs. Pathway analysis of a total of 252 differentially expressed proteins (DEPs) from the proteomic revealed that the immune response induced by TTT surgery at different stages was first comprehensively verified through multi-omics combined with immune biomarker analysis. The function of upward transport was activating the systemic immune response, and wound healing occurs with downward transport. The spatial metabolic characteristics of skin tissue from patients with DFUs indicated downregulated levels of stearoylcarnitine and the glycerophospholipid metabolism pathway in skin tissue from patients with severe DFUs. Finally, the expressions of PRNP (prion protein) to activate the immune response, PLCB3 (PLCB3, phospholipase C beta 3) and VE-cadherin to play roles in neovascularization, and PPDPF (pancreatic progenitor cell differentiation and proliferation factor), LAMC2 (laminin subunit gamma 2) and SPRR2G (small proline rich protein 2G) to facilitate the developmental process mainly keratinocyte differentiation were statistically significant in skin tissues through transcriptomic and RT-qPCR analysis.CONCLUSION: Tibial cortex transverse transport (TTT) surgery demonstrates favorable outcomes for patients with severe type 2 DFUs by activating a systemic immune response, contributing to anti-infection, ulcer recurrence, and the limb salvage rate for unilateral or bilateral DFUs. The specific clinical immune responses, candidate proteins, genes, and metabolic characteristics provide directions for in-depth mechanistic research on TTT surgery. Further research and public awareness are needed to optimize TTT surgery in patients with severe type 2 DFUs.PMID:38954658 | DOI:10.1097/JS9.0000000000001897

J Clin Invest. 2024 Jul 2:e179561. doi: 10.1172/JCI179561. Online ahead of print.ABSTRACTCytomegalovirus (CMV) is one of the most common and relevant opportunistic pathogens in immunocompromised individuals such as kidney transplant recipients (KTRs). The exact mechanisms underlying the disability of cytotoxic T cells to provide sufficient protection against CMV in immunosuppressed individuals have not been identified yet. Here, we performed in-depth metabolic profiling of CMV-specific CD8+ T cells in immunocompromised patients and show the development of metabolic dysregulation at the transcriptional, protein, and functional level of CMV-specific CD8+ T cells in KTRs with non-controlled CMV infection. These dysregulations comprise impaired glycolysis and increased mitochondrial stress, which is associated with an intensified expression of the nicotinamide adenine dinucleotide nucleotidase (NADase) CD38. Inhibiting NADase activity of CD38 reinvigorated the metabolism and improved cytokine production of CMV-specific CD8+ T cells. These findings were corroborated in a mouse model of CMV infection under conditions of immunosuppression. Thus, dysregulated metabolic states of CD8+ T cells could be targeted by inhibiting CD38 to reverse hypo-responsiveness in individuals who fail to control chronic viral infection.PMID:38954588 | DOI:10.1172/JCI179561

Clin Rev Allergy Immunol. 2024 Jul 2. doi: 10.1007/s12016-024-08995-3. Online ahead of print.ABSTRACTAtopic dermatitis and psoriasis are common chronic inflammatory diseases of high incidence that share some clinical features, including symptoms of pruritus and pain, scaly lesions, and histologically, acanthosis and hyperkeratosis. Meanwhile, they are both commonly comorbid with metabolic disorders such as obesity and diabetes, indicating that both diseases may exist with significant metabolic disturbances. Metabolomics reveals that both atopic dermatitis and psoriasis have abnormalities in a variety of metabolites, including lipids, amino acids, and glucose. Meanwhile, recent studies have highlighted the importance of the microbiome and its metabolites in the pathogenesis of atopic dermatitis and psoriasis. Metabolic alterations and microbiome dysbiosis can also affect the immune, inflammatory, and epidermal barrier, thereby influencing the development of atopic dermatitis and psoriasis. Focusing on the metabolic and microbiome levels, this review is devoted to elaborating the similarities and differences between atopic dermatitis and psoriasis, thus providing insights into the intricate relationship between both conditions.PMID:38954264 | DOI:10.1007/s12016-024-08995-3

Pediatr Cardiol. 2024 Jul 2. doi: 10.1007/s00246-024-03546-1. Online ahead of print.ABSTRACTPlasma exchange is an effective treatment for Kawasaki disease (KD), suggesting that plasma from patients with KD bears its causative agents. The aim of this study was to use mass spectrometry to identify candidate agents in patient sera. Serum samples were obtained from 17 KD patients. In six patients, samples were collected in each of three phases: the acute phase prior to acetylsalicylic acid (ASA) and intravenous immunoglobulin administration (Phase A1), the remission phase with ASA (Phase A2), and the remission phase without any medication (Phase A3). Sera from the remaining 11 patients were collected during Phases A1 and A2. The study also included two age- and gender-matched control groups, one with eight afebrile children and one with eight febrile children diagnosed with infectious disease. Patients in Phase A1 and febrile controls did not differ in body temperature, white blood cell counts, or C-reactive protein levels. Mass spectrometry analysis revealed that the intensity levels of m/z 9416, identified as apolipoprotein CIII (Apo CIII), were lower in Phase A1 samples compared with samples from patients in Phases A2 and A3, and from febrile controls (all comparisons, p < 0.01). Serum Apo CIII levels were also lower in Phase A1 samples compared with samples from Phase A2 patients and afebrile controls (both p < 0.01), but samples from patients in Phase A2 did not differ significantly from those of the afebrile controls (p = 0.55). This study demonstrated that serum Apo CIII level was decreased in the acute phase of KD.PMID:38953952 | DOI:10.1007/s00246-024-03546-1

mBio. 2024 Jul 2:e0152424. doi: 10.1128/mbio.01524-24. Online ahead of print.ABSTRACTThe hydroxyacid glycolate is a highly abundant carbon source in the environment. Glycolate is produced by unicellular photosynthetic organisms and excreted at petagram scales to the environment, where it serves as growth substrate for heterotrophic bacteria. In microbial metabolism, glycolate is first oxidized to glyoxylate by the enzyme glycolate oxidase. The recently described β-hydroxyaspartate cycle (BHAC) subsequently mediates the carbon-neutral assimilation of glyoxylate into central metabolism in ubiquitous Alpha- and Gammaproteobacteria. Although the reaction sequence of the BHAC was elucidated in Paracoccus denitrificans, little is known about the regulation of glycolate and glyoxylate assimilation in this relevant alphaproteobacterial model organism. Here, we show that regulation of glycolate metabolism in P. denitrificans is surprisingly complex, involving two regulators, the IclR-type transcription factor BhcR that acts as an activator for the BHAC gene cluster, and the GntR-type transcriptional regulator GlcR, a previously unidentified repressor that controls the production of glycolate oxidase. Furthermore, an additional layer of regulation is exerted at the global level, which involves the transcriptional regulator CceR that controls the switch between glycolysis and gluconeogenesis in P. denitrificans. Together, these regulators control glycolate metabolism in P. denitrificans, allowing the organism to assimilate glycolate together with other carbon substrates in a simultaneous fashion, rather than sequentially. Our results show that the metabolic network of Alphaproteobacteria shows a high degree of flexibility to react to the availability of multiple substrates in the environment.IMPORTANCEAlgae perform ca. 50% of the photosynthetic carbon dioxide fixation on our planet. In the process, they release the two-carbon molecule glycolate. Due to the abundance of algae, massive amounts of glycolate are released. Therefore, this molecule is available as a source of carbon for bacteria in the environment. Here, we describe the regulation of glycolate metabolism in the model organism Paracoccus denitrificans. This bacterium uses the recently characterized β-hydroxyaspartate cycle to assimilate glycolate in a carbon- and energy-efficient manner. We found that glycolate assimilation is dynamically controlled by three different transcriptional regulators: GlcR, BhcR, and CceR. This allows P. denitrificans to assimilate glycolate together with other carbon substrates in a simultaneous fashion. Overall, this flexible and multi-layered regulation of glycolate metabolism in P. denitrificans represents a resource-efficient strategy to make optimal use of this globally abundant molecule under fluctuating environmental conditions.PMID:38953632 | DOI:10.1128/mbio.01524-24

J Agric Food Chem. 2024 Jul 2. doi: 10.1021/acs.jafc.4c02316. Online ahead of print.ABSTRACTPea-protein-based ingredients are gaining attention in the food industry due to their nutritional benefits and versatility, but their bitter, astringent, green, and beany off-flavors pose challenges. This study applied fermentation using microbial cultures to enhance the sensory qualities of pea-protein-based beverages. Using UHPLC-TOF-MS analyses along with sensory profile comparisons, microbial species such as Limosilactobacillus fermentum, Lactococcus lactis, Lactobacillus johnsonii, Lacticaseibacillus rhamnosus, and Bifidobacterium longum were preselected from an entire culture collection and found to be effective in improving the overall flavor impression by reducing bitter off-notes and enhancing aroma profiles. Notably, L. johnsonii NCC533 and L. fermentum NCC660 exhibited controlled proteolytic activities after 48 h of fermentation, enriching the matrix with taste-active amino acids, nucleotides, and peptides and improving umami and salty flavors while mitigating bitterness. This study has extended traditional volatile analyses, including nonvolatile metabolomic, proteomic, and sensory analyses and offering a detailed view of fermentation-induced biotransformations in pea-protein-based food. The results highlight the importance of combining comprehensive screening approaches and sensoproteomic techniques in developing tastier and more palatable plant-based protein products.PMID:38953212 | DOI:10.1021/acs.jafc.4c02316

Front Pharmacol. 2024 Jun 17;15:1406493. doi: 10.3389/fphar.2024.1406493. eCollection 2024.ABSTRACTBACKGROUND: Ezetimibe, which lowers cholesterol by blocking the intestinal cholesterol transporter Niemann-Pick C1 like 1, is reported to reduce hepatic steatosis in humans and animals. Here, we demonstrate the changes in hepatic metabolites and lipids and explain the underlying mechanism of ezetimibe in hepatic steatosis.METHODS: We fed Otsuka Long-Evans Tokushima Fatty (OLETF) rats a high-fat diet (60 kcal % fat) with or vehicle (control) or ezetimibe (10 mg kg-1) via stomach gavage for 12 weeks and performed comprehensive metabolomic and lipidomic profiling of liver tissue. We used rat liver tissues, HepG2 hepatoma cell lines, and siRNA to explore the underlying mechanism.RESULTS: In OLETF rats on a high-fat diet, ezetimibe showed improvements in metabolic parameters and reduction in hepatic fat accumulation. The comprehensive metabolomic and lipidomic profiling revealed significant changes in phospholipids, particularly phosphatidylcholines (PC), and alterations in the fatty acyl-chain composition in hepatic PCs. Further analyses involving gene expression and triglyceride assessments in rat liver tissues, HepG2 hepatoma cell lines, and siRNA experiments unveiled that ezetimibe's mechanism involves the upregulation of key phospholipid biosynthesis genes, CTP:phosphocholine cytidylyltransferase alpha and phosphatidylethanolamine N-methyl-transferase, and the phospholipid remodeling gene lysophosphatidylcholine acyltransferase 3.CONCLUSION: This study demonstrate that ezetimibe improves metabolic parameters and reduces hepatic fat accumulation by influencing the composition and levels of phospholipids, specifically phosphatidylcholines, and by upregulating genes related to phospholipid biosynthesis and remodeling. These findings provide valuable insights into the molecular pathways through which ezetimibe mitigates hepatic fat accumulation, emphasizing the role of phospholipid metabolism.PMID:38953111 | PMC:PMC11215075 | DOI:10.3389/fphar.2024.1406493

Data Brief. 2024 May 28;55:110562. doi: 10.1016/j.dib.2024.110562. eCollection 2024 Aug.ABSTRACTDespite epidemiological indications, utility of metformin in liver cancer remains debated and the understanding of the mechanism underlying its anti-cancer effects remains incomplete. Particularly, whether it operates via similar mechanism under glucose-sufficient and glucose- deficient environments or whether these effects are reversible remains unexplored. This metabolomic dataset was collected from liver cancer (HepG2) cells treated with metformin or placebo over a period of 3 h to 48 h as well as from cells recovering after metformin withdrawal. Cells were exposed to placebo or 2.5 mM metformin with or without glucose (5 mM) supplementation. The cells were harvested at 3, 6, 12, 24, and 48 h post-treatment. Cells were also harvested after 24 h of treatment under one of these conditions followed by reversal of glucose and/or metformin exposure status for 48 h. Metabolites from six biological replicates of each experimental group were extracted using chilled monophasic metabolite extraction solvent (Water: Acetonitrile: Isopropanol= 2:3:3) containing homovanillic acid as an internal standard. Samples were derivatized using MOX reagent followed by MSTFA. Untargeted metabolomic profiling of derivatized samples were performed using an Agilent 7890B gas chromatograph coupled to a 5977B single quadrupole mass spectrometer. Analytes were injected through a splitless liner and separated on a HP-5MS ultra-inert column using ultrapure helium as the carrier gas. Peak alignment, annotation, and integration were done using Agilent MassHunter Quantitative analysis software. Multivariate analysis was performed using MetaboAnalyst 5.0. These experiments were performed to unravel the longitudinal evolution of cellular metabolome in response to metformin treatment, its glucose dependence, as well as to examine the reversibility of these changes. The dataset can help to identify glucose-independent pathways involved in anti-cancer effect of metformin. The dataset can be used to design experiments to develop novel therapeutic combinations synergistically acting with metformin to cripple the metabolic fitness of cancer cells. It can also help to develop experiments to test the effect of metformin withdrawal in liver cancer.PMID:38952952 | PMC:PMC11214992 | DOI:10.1016/j.dib.2024.110562

Front Plant Sci. 2024 Jun 17;15:1411471. doi: 10.3389/fpls.2024.1411471. eCollection 2024.ABSTRACTINTRODUCTION: Huperzia serrata is a traditional Chinese herb that has gained much attention for its production of Huperzine A (HupA). HupA has shown promise on treating Alzheimer's disease (AD). However, the biosynthetic pathway and molecular mechanism of HupA in H. serrata are still not well understood.METHODS: Integrated transcriptome and metabolome analysis was performed to reveal the molecular mechanisms related to HupA biosynthesis and antioxidant activity in Huperzia serrata.RESULTS: HT (in vitro H. serrata thallus) exhibits higher antioxidant activity and lower cytotoxicity than WH (wild H. serrata). Through hierarchical clustering analysis and qRT-PCR verification, 7 important enzyme genes and 13 transcription factors (TFs) related to HupA biosynthesis were detected. Among them, the average |log2FC| value of CYP (Cytochrome P450) and CAO (Copper amine oxidase) was the largest. Metabolomic analysis identified 12 metabolites involved in the HupA biosynthesis and 29 metabolites related to antioxidant activity. KEGG co-enrichment analysis revealed that tropane, piperidine and pyridine alkaloid biosynthesis were involved in the HupA biosynthesis pathway. Furthermore, the phenylpropanoid, phenylalanine, and flavonoid biosynthesis pathway were found to regulate the antioxidant activity of H. serrata. The study also identified seven important genes related to the regulation of antioxidant activity, including PrAO (primary-amine oxidase). Based on the above joint analysis, the biosynthetic pathway of HupA and potential mechanisms of antioxidant in H. serrata was constructed.DISCUSSION: Through differential transcriptome and metabolome analysis, DEGs and DAMs involved in HupA biosynthesis and antioxidant-related were identified, and the potential metabolic pathway related to HupA biosynthesis and antioxidant in Huperzia serrata were constructed. This study would provide valuable insights into the HupA biosynthesis mechanism and the H. serrata thallus medicinal value.PMID:38952843 | PMC:PMC11215074 | DOI:10.3389/fpls.2024.1411471

bioRxiv [Preprint]. 2024 May 23:2024.05.22.595414. doi: 10.1101/2024.05.22.595414.ABSTRACTCOVID-19 significantly decreases amino acids, fatty acids, and most eicosanoidsSARS-CoV-2 preferentially localizes to central lung tissueMetabolic disturbance is highest in peripheral tissue, not central like viral loadSpatial metabolomics allows detection of metabolites not altered overallSARS-CoV-2, the virus responsible for COVID-19, is a highly contagious virus that can lead to hospitalization and death. COVID-19 is characterized by its involvement in the lungs, particularly the lower lobes. To improve patient outcomes and treatment options, a better understanding of how SARS-CoV-2 impacts the body, particularly the lower respiratory system, is required. In this study, we sought to understand the spatial impact of COVID-19 on the lungs of mice infected with mouse-adapted SARS2-N501Y MA30 . Overall, infection caused a decrease in fatty acids, amino acids, and most eicosanoids. When analyzed by segment, viral loads were highest in central lung tissue, while metabolic disturbance was highest in peripheral tissue. Infected peripheral lung tissue was characterized by lower levels of fatty acids and amino acids when compared to central lung tissue. This study highlights the spatial impacts of SARS-CoV-2 and helps explain why peripheral lung tissue is most damaged by COVID-19.PMID:38952797 | PMC:PMC11216382 | DOI:10.1101/2024.05.22.595414

medRxiv [Preprint]. 2024 Jun 1:2024.05.31.24308233. doi: 10.1101/2024.05.31.24308233.ABSTRACTBACKGROUND: The immunometabolic mechanisms underlying variable responses to oral immunotherapy (OIT) in patients with IgE-mediated food allergy are unknown.OBJECTIVE: To identify novel pathways associated with tolerance in food allergy, we used metabolomic profiling to find pathways important for food allergy in multi-ethnic cohorts and responses to OIT.METHODS: Untargeted plasma metabolomics data were generated from the VDAART healthy infant cohort (N=384), a Costa Rican cohort of children with asthma (N=1040), and a peanut OIT trial (N=20) evaluating sustained unresponsiveness (SU, protection that lasts after therapy) versus transient desensitization (TD, protection that ends immediately afterwards). Generalized linear regression modeling and pathway enrichment analysis identified metabolites associated with food allergy and OIT outcomes.RESULTS: Compared with unaffected children, those with food allergy were more likely to have metabolomic profiles with altered histidines and increased bile acids. Eicosanoids (e.g., arachidonic acid derivatives) (q=2.4×10 -20 ) and linoleic acid derivatives (q=3.8×10 -5 ) pathways decreased over time on OIT. Comparing SU versus TD revealed differing concentrations of bile acids (q=4.1×10 -8 ), eicosanoids (q=7.9×10 -7 ), and histidine pathways (q=0.015). In particular, the bile acid lithocholate (4.97[1.93,16.14], p=0.0027), the eicosanoid leukotriene B4 (3.21[1.38,8.38], p=0.01), and the histidine metabolite urocanic acid (22.13[3.98,194.67], p=0.0015) were higher in SU.CONCLUSIONS: We observed distinct profiles of bile acids, histidines, and eicosanoids that vary among patients with food allergy, over time on OIT and between SU and TD. Participants with SU had higher levels of metabolites such as lithocholate and urocanic acid, which have immunomodulatory roles in key T-cell subsets, suggesting potential mechanisms of tolerance in immunotherapy.KEY MESSAGES: - Compared with unaffected controls, children with food allergy demonstrated higher levels of bile acids and distinct histidine/urocanic acid profiles, suggesting a potential role of these metabolites in food allergy. - In participants receiving oral immunotherapy for food allergy, those who were able to maintain tolerance-even after stopping therapyhad lower overall levels of bile acid and histidine metabolites, with the exception of lithocholic acid and urocanic acid, two metabolites that have roles in T cell differentiation that may increase the likelihood of remission in immunotherapy.CAPSULE SUMMARY: This is the first study of plasma metabolomic profiles of responses to OIT in individuals with IgE-mediated food allergy. Identification of immunomodulatory metabolites in allergic tolerance may help identify mechanisms of tolerance and guide future therapeutic development.PMID:38952781 | PMC:PMC11216533 | DOI:10.1101/2024.05.31.24308233

Vavilovskii Zhurnal Genet Selektsii. 2024 Jun;28(3):299-307. doi: 10.18699/vjgb-24-34.ABSTRACTThe diversity of pathogenetic mechanisms underlying arterial hypertension leads to the necessity to devise a personalized approach to the diagnosis and treatment of the disease. Metabolomics is one of the promising methods for personalized medicine, as it provides a comprehensive understanding of the physiological processes occurring in the body. The metabolome is a set of low-molecular substances available for detection in a sample and representing intermediate and final products of cell metabolism. Changes in the content and ratio of metabolites in the sample mark the corresponding pathogenetic mechanisms by highlighting them, which is especially important for such a multifactorial disease as arterial hypertension. To identify metabolomic markers for hypertensive conditions of different origins, three forms of arterial hypertension (AH) were studied: rats with hereditary AH (ISIAH rat strain); rats with AH induced by L-NAME administration (a model of endothelial dysfunction with impaired NO production); rats with AH caused by the administration of deoxycorticosterone in combination with salt loading (hormone-dependent form - DOCA-salt AH). WAG rats were used as normotensive controls. 24-hour urine samples were collected from all animals and analyzed by quantitative NMR spectroscopy for metabolic profiling. Then, potential metabolomic markers for the studied forms of hypertensive conditions were identified using multivariate statistics. Analysis of the data obtained showed that hereditary stress-induced arterial hypertension in ISIAH rats was characterized by a decrease in the following urine metabolites: nicotinamide and 1-methylnicotinamide (markers of inflammatory processes), N- acetylglutamate (nitric oxide cycle), isobutyrate and methyl acetoacetate (gut microbiota). Pharmacologically induced forms of hypertension (the L-NAME and DOCA+NaCl groups) do not share metabolomic markers with hereditary AH. They are differentiated by N,N-dimethylglycine (both groups), choline (the L-NAME group) and 1-methylnicotinamide (the group of rats with DOCA-salt hypertension).PMID:38952704 | PMC:PMC11214897 | DOI:10.18699/vjgb-24-34

J Biomed Opt. 2024 Jun;29(Suppl 2):S22711. doi: 10.1117/1.JBO.29.S2.S22711. Epub 2024 Jul 1.ABSTRACTSIGNIFICANCE: Biomanufacturing utilizes modified microbial systems to sustainably produce commercially important biomolecules for use in agricultural, energy, food, material, and pharmaceutical industries. However, technological challenges related to non-destructive and high-throughput metabolite screening need to be addressed to fully unlock the potential of synthetic biology and sustainable biomanufacturing.AIM: This perspective outlines current analytical screening tools used in industrial cell strain development programs and introduces label-free vibrational spectro-microscopy as an alternative contrast mechanism.APPROACH: We provide an overview of the analytical instrumentation currently used in the "test" portion of the design, build, test, and learn cycle of synthetic biology. We then highlight recent progress in Raman scattering and infrared absorption imaging techniques, which have enabled improved molecular specificity and sensitivity.RESULTS: Recent developments in high-resolution chemical imaging methods allow for greater throughput without compromising the image contrast. We provide a roadmap of future work needed to support integration with microfluidics for rapid screening at the single-cell level.CONCLUSIONS: Quantifying the net expression of metabolites allows for the identification of cells with metabolic pathways that result in increased biomolecule production, which is essential for improving the yield and reducing the cost of industrial biomanufacturing. Technological advancements in vibrational microscopy instrumentation will greatly benefit biofoundries as a complementary approach for non-destructive cell screening.PMID:38952688 | PMC:PMC11216725 | DOI:10.1117/1.JBO.29.S2.S22711

Front Microbiol. 2024 Jun 17;15:1433047. doi: 10.3389/fmicb.2024.1433047. eCollection 2024.ABSTRACT[This corrects the article DOI: 10.3389/fmicb.2024.1334045.].PMID:38952449 | PMC:PMC11216365 | DOI:10.3389/fmicb.2024.1433047

Heliyon. 2024 Jun 6;10(12):e32523. doi: 10.1016/j.heliyon.2024.e32523. eCollection 2024 Jun 30.ABSTRACTRhamnus utilis Decne. (Family Rhamnaceae Juss.) leaf is commonly prepared as a anti-inflammatory herbal medicine and used for tea production. To investigate the mechanism of Rhamnus utilis Decne. aqueous extract (RDAE) against acute alcoholic liver disease (ALD) in mice. The ALD mouse (Male ICR) model was induced via intragastric administration of 52 % alcohol. Mice in each group were treated by gavage once daily with the RDAE (1.12, 2.25, 4.500 g/kg). The expression of proteins involved in the MAPKs/NF-κB/COX-2-iNOS pathway was measured by western blotting. Non-targeted metabolomics was used to determine metabolic profiles and critical pathways, while targeted metabolomics validated key amino acid metabolites. After administration of RDAE, the body mass of mice was significantly increased. The liver index was significantly decreased. Meanwhile, the serum levels of AST, ALT, TG, TC, MDA, TNF-α, IL-1β and IL-6 were significantly decreased (P < 0.05, P < 0.01), but GSH level was inversely increased (P < 0.05). Metabolomic analysis revealed nine major pathways involved in the therapeutic effect of RDAE, including fructose and mannose metabolism. The levels of 7 amino acids including leucine, proline and alanine/sarcosine were significantly upregulated. Additionally, protein levels of p-NF-κB (p65)/NF-κB (p65), p-ERK1/2/ERK1/2, p-JNK/JNK, p-p38/p38, COX-2 and iNOS were significantly decreased (P < 0.01, P < 0.05). RDAE is used to treat acute ALD by improving lipid metabolism, inhibiting the expression of pro-inflammatory cytokines and regulating MAPKs/NF-κB/COX-2-iNOS signalling pathway. These findings provide valuable insights for acute ALD therapy based on traditional Chinese medicine (TCM).PMID:38952369 | PMC:PMC11215275 | DOI:10.1016/j.heliyon.2024.e32523

J Sci Food Agric. 2024 Jul 2. doi: 10.1002/jsfa.13691. Online ahead of print.ABSTRACTBACKGROUND: This study aimed to elucidate the mechanism of oleuropein (OLE) ameliorates non-alcoholic fatty liver disease (NAFLD) and its underlying mechanisms.RESULTS: Male C57BL/6J mice were fed either a low-fat diet (LFD), a high-fat diet (HFD), or a HFD supplemented with 0.03% (w/w) OLE for 16 weeks. OLE supplementation decreased body weight and liver weight, improved serum lipid profiles, and ameliorated HFD-induced hepatic dysfunction. Liver metabolomics analysis revealed that OLE increased the levels of nicotinamide, tauroursodeoxycholic acid, taurine, and docosahexaenoic acid, which were beneficial for lipid homeostasis and inflammation regulation. OLE exerted its protective effects by activating peroxisome proliferator-activated receptor alpha (PPARα), a key transcription factor that regulates fibroblast growth factor 21 (FGF21) expression and modulates lipid oxidation, lipogenesis and inflammation pathways. Importantly, OLE supplementation did not significantly affect body weight or liver weight in PPARα knockout (PPARα KO) mice, indicating that PPARα is essential for OLE-mediated NAFLD prevention.CONCLUSION: Our results suggest that OLE alleviates NAFLD in mice by activating PPARα and modulating liver metabolites. © 2024 Society of Chemical Industry.PMID:38952322 | DOI:10.1002/jsfa.13691