PubMed

Sci China Life Sci. 2024 Dec 18. doi: 10.1007/s11427-024-2779-9. Online ahead of print.ABSTRACTProlonged exposure to high-altitude environments may increase the risk of cognitive decline in young migrants. Recent studies suggest that hypobaric hypoxia-induced alterations in gut microbial composition could partly contribute to this risk. However, the absence of direct evidence from cohort studies and an unclear mechanism hinder intervention development based on this hypothesis. This study recruited 109 young male migrants living in Xizang to investigate the microbial mechanisms underlying cognitive impairment associated with high-altitude migration. Multi-omic analysis revealed distinct microbiome and metabolome features in migrants with cognitive decline, notably a reduced abundance of Clostridium species and disrupted fecal absorption of L-valine. Mechanistic studies showed that hypobaric hypoxia significantly damaged the intestinal barrier, leading to lipopolysaccharide (LPS) leakage and an influx of inflammatory factors into the peripheral blood, which activated microglia and caused neuronal injury in the hippocampus of mice. Additionally, compromised L-valine absorption due to intestinal barrier damage correlated with lower hippocampal glutamate levels and neurotrophic factors. Intervention with Clostridium sp. effectively restored the intestinal barrier and enhanced L-valine absorption, which mitigated hypobaric hypoxia-induced inflammation and hippocampal neural damage in mice. In conclusion, cognitive impairment among young migrants at high altitude may be attributed to hypobaric hypoxia-induced gut microbiota disruption and subsequent intestinal barrier dysfunction. This study may provide a promising approach for preventing and treating high-altitude-associated cognitive impairment.PMID:39704932 | DOI:10.1007/s11427-024-2779-9

J Neurooncol. 2024 Dec 20. doi: 10.1007/s11060-024-04902-0. Online ahead of print.ABSTRACTPURPOSE: To review applications of cerebral spinal fluid (CSF) biomarkers for the diagnosis, monitoring and treatment of leptomeningeal metastatic disease (LMD) among patients with metastatic solid tumors.METHODS: A narrative review identified original research related to CSF biomarkers among patients with metastatic solid tumors and LMD. Pre-clinical research (e.g. studies conducted in animal models) was not included. A descriptive analysis of literature was undertaken, with a focus on clinical applications related to the diagnosis, monitoring and treatment of LMD.RESULTS: The low cellularity of CSF in comparison to plasma is an advantage for liquid biopsy, given that circulating tumor DNA (ctDNA) is not significantly diluted by genomic DNA from non-cancer cells. This results in higher variant allelic frequencies and increased sensitivity in detecting ctDNA compared to plasma. However, the clinical significance of positive ctDNA and/or circulating tumor cells (CTCs) in the CSF, particularly in the absence of other signs of LMD (either clinical and/or radiological), remains unclear. While the use of CSF liquid biopsy to monitor treatment response is promising, this approach requires prospective validation using larger sample sizes prior to adoption in routine clinical care. Discovery efforts involving proteomics and metabolomics have potential to identify proteins involved in the regulation of energy metabolism, vasculature, and inflammation in LMD, which in turn, may offer insights into novel treatment approaches.CONCLUSION: CSF liquid biopsy should be incorporated in prospective studies for patients with LMD to validate promising diagnostic and/or predictive biomarkers of treatment response, as well as new therapeutic targets.PMID:39704899 | DOI:10.1007/s11060-024-04902-0

Plant Cell Rep. 2024 Dec 20;44(1):8. doi: 10.1007/s00299-024-03399-1.ABSTRACTN-Sulfonated IAA was discovered as a novel auxin metabolite in Urtica where it is biosynthesized de novo utilizing inorganic sulfate. It showed no auxin activity in DR5::GUS assay, implying possible inactivation/storage mechanism. A novel auxin derivative, N-sulfoindole-3-acetic acid (IAA-N-SO3H, SIAA), was discovered in stinging nettle (Urtica dioica) among 116 sulfonated metabolites putatively identified by a semi-targeted UHPLC-QqTOF-MS analysis of 23 plant/algae/fungi species. These sulfometabolites were detected based on the presence of a neutral loss of sulfur trioxide, as indicated by the m/z difference of 79.9568 Da in the MS2 spectra. The structure of newly discovered SIAA was confirmed by synthesizing its standard and comparing retention time, m/z and MS2 spectrum with those of SIAA found in Urtica. To study its natural occurrence, 73 species in total were further analyzed by UHPLC-QqTOF-MS or targeted UHPLC-MS/MS method with a limit of detection of 244 fmol/g dry weight. However, SIAA was only detected in Urtica at a concentration of 13.906 ± 9.603 nmol/g dry weight. Its concentration was > 30 times higher than that of indole-3-acetic acid (IAA), and the SIAA/IAA ratio was further increased under different light conditions, especially in continuous blue light. In addition to SIAA, structurally similar metabolites, N-sulfoindole-3-lactic acid, 4-(sulfooxy)phenyllactic acid and 4-(sulfooxy)phenylacetic acid, were detected in Urtica for the first time. SIAA was biosynthesized from inorganic sulfate in seedlings, as confirmed by the incorporation of exogenous 34S-ammonium sulfate (1 mM and 10 mM). SIAA exhibited no auxin activity, as demonstrated by both the Arabidopsis DR5::GUS assay and the Arabidopsis phenotype analysis. Sulfonation of IAA may therefore be a mechanism for IAA deactivation and/or storage in Urtica, similar to sulfonation of the jasmonates in Arabidopsis.PMID:39704813 | DOI:10.1007/s00299-024-03399-1

ACS Nano. 2024 Dec 20. doi: 10.1021/acsnano.4c11505. Online ahead of print.ABSTRACTSpatial omics methods are extensions of traditional histological methods that can illuminate important biomedical mechanisms of physiology and disease by examining the distribution of biomolecules, including nucleic acids, proteins, lipids, and metabolites, at microscale resolution within tissues or individual cells. Since, for some applications, the desired resolution for spatial omics approaches the nanometer scale, classical tools have inherent limitations when applied to spatial omics analyses, and they can measure only a limited number of targets. Nanotechnology applications have been instrumental in overcoming these bottlenecks. When nanometer-level resolution is needed for spatial omics, super resolution microscopy or detection imaging techniques, such as mass spectrometer imaging, are required to generate precise spatial images of target expression. DNA nanostructures are widely used in spatial omics for purposes such as nucleic acid detection, signal amplification, and DNA barcoding for target molecule labeling, underscoring advances in spatial omics. Other properties of nanotechnologies include advanced spatial omics methods, such as microfluidic chips and DNA barcodes. In this review, we describe how nanotechnologies have been applied to the development of spatial transcriptomics, proteomics, metabolomics, epigenomics, and multiomics approaches. We focus on how nanotechnology supports improved resolution and throughput of spatial omics, surpassing traditional techniques. We also summarize future challenges and opportunities for the application of nanotechnology to spatial omics methods.PMID:39704725 | DOI:10.1021/acsnano.4c11505

J Exp Med. 2025 Feb 3;222(2):e20240728. doi: 10.1084/jem.20240728. Epub 2024 Dec 20.ABSTRACTInvariant natural killer T (iNKT) cells are unconventional T cells recognizing lipid antigens in a CD1d-restricted manner. Among these lipid antigens, α-galactosylceramide (α-GalCer), which was originally identified in marine sponges, is the most potent antigen. Although the presence of α-anomeric hexosylceramide and microbiota-derived branched α-GalCer is reported, antigenic α-GalCer has not been identified in mammals. Here, we developed a high-resolution separation and detection system, supercritical fluid chromatography tandem mass spectrometry (SFC/MS/MS), that can discriminate hexosylceramide diastereomers (α-GalCer, α-GlcCer, β-GalCer, or β-GlcCer). The B16 melanoma tumor cell line does not activate iNKT cells; however, ectopic expression of CD1d was sufficient to activate iNKT cells without adding antigens. B16 melanoma was unlikely to generate iNKT cell antigens; instead, antigen activity was detected in cell culture serum. Activity-based purification and SFC/MS/MS identified dihydrosphingosine-based saturated α-GalCer as an antigenic component in serum, bile, and lymphoid tissues. These results show the first evidence for the presence of potent antigenic α-GalCer in mammals.PMID:39704712 | DOI:10.1084/jem.20240728

Physiol Plant. 2024 Nov-Dec;176(6):e70006. doi: 10.1111/ppl.70006.ABSTRACTMelatonin (MT) serves an indispensable function in plant development and their response to abiotic stress. Although numerous drought-tolerance genes have been ascertained in wheat, further investigation into the molecular pathways controlling drought stress tolerance remains necessary. In this investigation, it was observed that MT treatment markedly enhanced drought resistance in wheat by diminishing malondialdehyde (MDA) levels and augmenting the activity of antioxidant enzymes POD, APX, and CAT compared to untreated control plants. Transcriptomic analysis disclosed that melatonin treatment activated the tryptophan metabolism and flavonoid biosynthesis pathways. Furthermore, quantitative reverse transcription PCR (qRT-PCR) outcomes validated that the expression trends of these differentially expressed genes aligned with the transcriptomic data. Metabolomic profiling identified alterations in the abundance of several metabolites, including tryptamine, MT, formylanthranilate, 3-hydroxyanthranilate, 6-hydroxymelatonin, naringenin chalcone, astragalin, pinbanksin, and caffeoyl quinic acid. Co-expression analysis suggested that various transcription factors-encompassing AP2/ERF-ERF, WRKY, bZIP, C2H2, bHLH, NAC, and MYB-participated in controlling the differentially expressed genes across multiple pathways. Ultimately, these findings highlight that exogenous MT application bolsters wheat's drought tolerance through the modulation of tryptophan metabolism and flavonoid biosynthesis. These insights provide novel perspectives on the molecular frameworks mediating MT's effect on drought resistance and pinpointing candidate genes for potential genetic enhancement programs in wheat.PMID:39704497 | DOI:10.1111/ppl.70006

J Inherit Metab Dis. 2025 Jan;48(1):e12832. doi: 10.1002/jimd.12832.ABSTRACTX-linked adrenoleukodystrophy (ALD) is a peroxisomal disorder resulting from pathogenic variants in the ABCD1 gene that primarily affects the nervous system and is characterized by progressive axonal degeneration in the spinal cord and peripheral nerves and leukodystrophy. Dysfunction of peroxisomal very long-chain fatty acid (VLCFA) degradation has been implicated in ALD pathology, but the impact on astrocytes, which critically support neuronal function, remains poorly understood. Fibroblasts from four ALD patients were reprogrammed to generate human-induced pluripotent stem cells (hiPSC). hiPSC-derived astrocytes were generated to study the impact of ALD on astrocytic fatty acid homeostasis. Our study reveals significant changes in the lipidome of ALD hiPSC-derived astrocytes, characterized by an enrichment of VLCFAs across multiple lipid classes, including triacylglycerols, cholesteryl esters, and phosphatidylcholines. Importantly, ALD hiPSC-derived astrocytes not only exhibit intrinsic lipid dysregulation but also affect the dendritic tree complexity of neurons in co-culture systems. These findings highlight the cell-autonomous effects of pathogenic variants in the ABCD1 protein on astrocytes and their microenvironment, shed light on potential mechanisms underlying ALD neuropathology, and underscore the critical role of astrocytes in neuronal health.PMID:39704488 | DOI:10.1002/jimd.12832

Environ Sci Technol. 2024 Dec 20. doi: 10.1021/acs.est.4c07881. Online ahead of print.ABSTRACTFoliar application of beneficial nanoparticles exhibits potential in mitigating combined stresses from heavy metals and polycyclic aromatic hydrocarbons (PAHs) in crops, necessitating a comprehensive understanding of plant-rhizosphere-microbial processes to promote sustainable nanotechnology in agriculture. Herein, we investigated the mitigating mechanisms of foliar application of zinc oxide nanoparticles (nZnO) on lettuce growth under phenanthrene (Phe) and cadmium (Cd) costress. Compared to Phe + Cd treatment, low (L-nZnO) and high (H-nZnO) concentration of nZnO increased fresh biomass (27.2% and 8.42%) and root length (20.4% and 39.6%) and decreased MDA (35.0% and 40.0%) and H2O2 (29.0% and 15.6%) levels. L-nZnO and H-nZnO decreased Cd in roots (26.8% and 41.8%) and enhanced Zn in roots (19.9% and 107%), stems (221% and 2510%), and leaves (233% and 1500%), suggesting the long-distance migration of Zn from leaves to roots and subsequently regulating the metabolic pathways and microbial communities. Metabolomics revealed that nZnO modulated leaf glycerophospholipid metabolism and amino acid pathways and promoted rhizosphere soil carbon and phosphorus metabolism. Additionally, nZnO enriched the plant-growth-promoting, extreme, and stress-resistant bacteria in roots and leaves and heavy-metal-resistant and PAH-degrading bacteria in rhizosphere soil. These findings underscore the promising nanostrategy of nZnO to benefit plant growth in soil cocontaminated with heavy metals and PAHs.PMID:39704184 | DOI:10.1021/acs.est.4c07881

Haematologica. 2024 Dec 19. doi: 10.3324/haematol.2024.285154. Online ahead of print.ABSTRACTPlasma metabolomics analysis was performed on 44 patients with relapsed/refractory B-cell non-Hodgkin lymphoma (r/r/B-NHL) infused with approved CD19.CAR-T cell products at the time of pre-lymphodepletion (PLD) and at day +1, +7, and +30 after CAR-T cell infusion. At the PLD time point, a metabolic profile characterized by high lipoproteins and lactate and low glucose contributed to poor outcome prediction in association with high lactate dehydrogenase levels. At day+1, higher plasma levels of lipid metabolism products and lower glucose and glycoproteins levels were observed in tisa-cel compared to axi-cel-treated patients. At day+30, discriminant analysis found two clusters in a subgroup of patients, one with CR lasting one year after therapy, and another who relapsed within one year (relapsed>D30). This latter showed a higher content of N-GlycA, a known biomarker of systemic inflammation that is also correlated with C-reactive protein in our case setting of relapsing patients. Our data show complex metabolomic changes that track the evolution of the disease and drug activity in the first 30 days of CAR-T cell therapy. Conceivably, a pro-inflammatory drift may be linked to a forthcoming disease relapse in CAR-T patients.PMID:39704157 | DOI:10.3324/haematol.2024.285154

J Sci Food Agric. 2024 Dec 20. doi: 10.1002/jsfa.14084. Online ahead of print.ABSTRACTBACKGROUND: Alterations in the degrees of milling (DOM) could significantly influence the odor of rice. A gas chromatography-mass spectrometry (GC-MS)-based untargeted metabolomics method has been effectively employed to identify the differential volatiles among rice from various origins or varieties, although it has not been utilized to identify the differential volatiles among cooked rice with different DOM.RESULTS: Fifty volatile compounds were detected in cooked brown rice (CBR), cooked medium-milled rice (CMMR) and cooked well-milled rice (CWMR) of the four fragrant Simiao rice by GC-MS. A comprehensive GC-MS-based untargeted metabolomics analysis revealed 25 differential volatiles among CBR, CMMR and CWMR. Among them, seven differential volatiles, namely hexanal, octanal, decanal, (E,E)-2,4-decadienal, vanillin, acetoin and pentanol, as well as one differential volatile (dibutyl phthalate), were determined as volatile markers for CBR and CMMR, respectively. Moreover, acetoin was identified to distinguish among CBR, CMMR, and CWMR of fragrant Simiao rice.CONCLUSION: GC-MS-based untargeted metabolomics could be effectively applied to screen differential volatiles in cooked rice with different DOM. The 25 differential volatiles identified could significantly contribute to the distinctive odor in cooked fragrant Simiao rice with different DOM. © 2024 Society of Chemical Industry.PMID:39704026 | DOI:10.1002/jsfa.14084

Front Oncol. 2024 Dec 5;14:1418283. doi: 10.3389/fonc.2024.1418283. eCollection 2024.ABSTRACTBACKGROUND: Previous epidemiological studies have yielded inconclusive results regarding the causality between blood metabolites and the risk of gastric cancer (GC). To address this shortcoming, we conducted a two-sample Mendelian randomization (MR) study, combined with metabolomics techniques, to elucidate the causality between 486 genetically predicted blood metabolites and GC.METHODS: MR analysis and metabolomics techniques such as ultra-high performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) and gas chromatography/tandem mass spectrometry (GC-MS/MS) technologies were employed to assess the causality of 486 genetically predicted blood metabolites on the risk of GC. The genome-wide association study (GWAS) summary data for 486 blood metabolites from 7,824 individuals. The GWAS summary data for GC (ebi-a-GCST90018849) were obtained from the IEU Open GWAS project, including 1,029 GC cases and 474,841 controls. Primary causality estimates were obtained using inverse variance weighting (IVW), supplemented with the weighted median, MR-Egger, weighted mode, and simple mode. In addition, we conducted sensitivity analyses (including Cochran's Q, MR-Egger intercept, MR-PRESSO, and leave-one-out tests),Steiger's test, linked disequilibrium score regression, and multivariate MR (MVMR) to improve the assessment of causality between GC and blood metabolite. Finally, we recruited a total of 11 patients diagnosed with gastric cancer from the First Affiliated Hospital of Air Force Military Medical University between September and October 2024. The control group comprised 11 healthy individuals. Serum samples were collected from both groups for the evaluation of blood-related metabolite expression levels using advanced techniques such as ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and gas chromatography-mass spectrometry (GC-MS/MS).RESULTS: The MVMR analysis revealed a significant association between genetically predicted elevated levels of tryptophan (odds ratio [OR] = 0.523, 95% confidence interval [CI] = 0.313-0.872, p = 0.013), nonadecanoate (19:0) (odds ratio [OR] = 0.460, 95% confidence interval [CI] = 0.225-0.943, p = 0.034), and erythritol (odds ratio [OR] = 0.672, 95% confidence interval [CI] = 0.468-0.930, p = 0.016) with a decreased risk of gastric cancer. Based on metabolomic techniques such as UPLC-MS/MS and GC-MS/MS analyses, it has been demonstrated that the expression levels of tryptophan, nonadecanoate (19:0), and erythritol are reduced in patients with gastric cancer. This finding aligns with the results obtained from our MR analysis and provides further confirmation regarding the protective role of tryptophan, nonadecanoate (19:0), and erythritol against gastric cancer.CONCLUSIONS: These findings indicate that three blood metabolites are causally related to GC and provide new perspectives for combining genomics and metabolomics to study the mechanisms of metabolite-mediated GC development.PMID:39703854 | PMC:PMC11655336 | DOI:10.3389/fonc.2024.1418283

Front Oncol. 2024 Dec 5;14:1389529. doi: 10.3389/fonc.2024.1389529. eCollection 2024.ABSTRACTCentral nervous system (CNS) tumours are the most common cancer cause of death in under 40s in the UK, largely because they persist and recur and sometimes metastasise during treatment. Therefore, longitudinal monitoring of patients during and following treatment must be undertaken to understand the course of the disease and alter treatment plans reactively. This monitoring must be specific, sensitive, rapid, low cost, simple, and accepted by the patient. Cerebrospinal fluid (CSF) examination obtained following lumbar puncture, already a routine part of treatment in paediatric cases, could be better utilised with improved biomarkers. In this review, we discuss the potential for metabolites in the CSF to be used as biomarkers of CNS tumour remission, progression, response to drugs, recurrence and metastasis. We confer the clinical benefits and risks of this approach and conclude that there are many potential advantages over other tests and the required instrumentation is already present in UK hospitals. On the other hand, the approach needs more research investment to find more metabolite biomarkers, better understand their relation to the tumour, and validate those biomarkers in a standardised assay in order for the assay to become a clinical reality.PMID:39703845 | PMC:PMC11655469 | DOI:10.3389/fonc.2024.1389529

Int J Gen Med. 2024 Dec 14;17:6229-6241. doi: 10.2147/IJGM.S498965. eCollection 2024.ABSTRACTOBJECTIVE: To explore the types of pathogens causing lower respiratory tract infections (LTRIs) in children and construction of a predictive model for monitoring secondary asthma caused by LTRIs.METHODS: Seven hundred and seventy-five children with LTRIs treated from June 2017 to July 2024 were selected as research subjects. Bacterial isolation and culture were performed on all children, and drug sensitivity tests were conducted on the isolated pathogens; And according to whether the child developed secondary asthma during treatment, they were divided into asthma group (n = 116) and non-asthma group (n = 659); Using logistic regression model to analyze the risk factors affecting secondary asthma in children with LTRIs, and establishing machine learning (ie nomogram and decision tree) prediction models; Using ROC curve analysis machine learning algorithms to predict AUC values, sensitivity, and specificity of secondary asthma in children with LTRIs.RESULTS: 792 pathogenic bacteria were isolated from 775 children with LTRIs through bacterial culture, including 261 Gram positive bacteria (32.95%) and 531 Gram negative bacteria (67.05%). Logistic regression model analysis showed that Glycerophospholipids, Sphingolipids and radiomics characteristics were risk factors for secondary asthma in children with LTRIs (P < 0.05). The AUC, sensitivity, and specificity of nomogram prediction for secondary asthma in children with LTRIs were 0.817(95CI: 0.760-0.874), 82.3%, and 76.6%, respectively; The AUC of decision tree prediction for secondary asthma in children with LTRIs is 0.926(95% CI: 0.869-0.983), with a sensitivity of 96.7% and a specificity of 87.8%.CONCLUSION: LTRIs in children are mainly caused by Staphylococcus aureus, Streptococcus pneumoniae, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa; In addition, machine learning combined with multi-omics prediction models has shown good ability in predicting LTRIs combined with asthma, providing a non-invasive and effective method for clinical decision-making.PMID:39703797 | PMC:PMC11656193 | DOI:10.2147/IJGM.S498965

Physiol Plant. 2024 Nov-Dec;176(6):e70016. doi: 10.1111/ppl.70016.ABSTRACTPlant-derived nanovesicles (PDNVs) and extracellular vesicles (EVs) represent a promising area of research due to their unique properties and potential therapeutic applications. Pinellia ternata (P. ternata) is well-known for its pharmacological properties but the PDNVs and EVs derived from it have been largely understudied. Previous studies have shown that a Temporary Immersion Bioreactor System (TIBS) plays an important role in controlling plant growth in order to obtain reproducible EVs and PDNVs. PDNVs were isolated from P. ternata plants and EVs were collected in the TIBS medium via ultra-high-speed differential centrifugation. Particle size, Zeta potentials and particle concentrations were assessed for PDNVs and EVs. Furthermore, non-targeted metabolomics was used to assess metabolic compositional differences between EVs and PDNVs, enabling the evaluation of the TIBS's quality control efficacy. Metabolomic profiling revealed 1072 metabolites in PDNVs and EVs, including 426 differential metabolites (DMs) distinguishing PDNVs from EVs: 362 DMs were positively correlated with PDNVs and 64 DMs were positively correlated with EVs; they were enriched across 17 KEGG pathways. PCA, PLS-DA, and metabolite sample correlation analyses showed high consistency between the replicates (PDNVs >0.87, EVs >0.93). This study demonstrated that TIBS is a performant system allowing consistency in generating PDNVs and EVs from P. ternata. We also highlighted the metabolic differences between PDNVs and EVs, guiding researchers in finding the bet system to produce efficient nanodrugs containing P. ternata pharmacological compounds.PMID:39703077 | DOI:10.1111/ppl.70016

Physiol Plant. 2024 Nov-Dec;176(6):e70021. doi: 10.1111/ppl.70021.ABSTRACTUrban vegetation provides many ecosystem services like heat island mitigation. However, urban trees are subjected to the stresses that they are meant to alleviate, with drought being a main constraint. We investigated the drought response strategy of plane trees (Platanus × hispanica), focusing on stomatal regulation and metabolic remodelling. To address this question, a semi-controlled experiment was performed in an urban site with fourteen plane trees grown in containers. From May to June 2022, those trees were physiologically characterized in response to a controlled edaphic drought completed by a targeted metabolome analysis focused on amino acids, sugars, polyols and organic acids. Early P. × hispanica response to drought consisted in stomatal closure limiting carbon assimilation and osmotic adjustment, which was likely related to malate and trehalose accumulation. Both allowed the maintenance of stem water potential and Relative Water Content. As the drought became severe, when the extractable soil water content (eSWC) dropped below 30%, a non-stomatal limitation of photosynthesis was observed and was associated with photosynthetic apparatus damage (reduced chlorophyll content and decrease in Fv/Fm) and a further decline in carbon assimilation. When eSWC decreased below 25%, severe drought induced defoliation. Together, these results highlight the isohydric strategy of P. × hispanica, based notably on osmotic adjustment and explain its resistance to drought combined with other urban constraints. In the context of climatic change in cities, it would be interesting to analyse the impact of successive drought cycles in the long term, aiming for sustainable planning and management of urban trees.PMID:39703071 | DOI:10.1111/ppl.70021

Mol Plant. 2024 Dec 18:S1674-2052(24)00394-0. doi: 10.1016/j.molp.2024.12.010. Online ahead of print.ABSTRACTAngraecum sesquipedale, also known as Darwin's orchid, possesses an exceptionally long nectar spur. Charles Darwin predicted the orchid to be pollinated by a hawkmoth with a correspondingly long proboscis, later identified as Xanthopan praedicta. In this plant-pollinator interaction, the A. sesquipedale flower emits a complex blend of scent compounds dominated by diurnally regulated oximes (R1R2C=N-OH) to attract crepuscular and nocturnal pollinators. The molecular mechanism of oxime biosynthesis remains unclear in orchids. Here, we present the chromosome-level genome of A. sesquipedale. The haploid genome size is 2.10 Gb and represents 19 pseudochromosomes. Cytochrome P450 encoding genes of the CYP79 family known to be involved in oxime biosynthesis in seed plants are not present in the A. sesquipedale genome nor in the genomes of other members of the orchid family. Metabolomic analysis of the A. sesquipedale flower revealed a substantial release of oximes at dusk during the blooming stage. By integrating metabolomic and transcriptomic correlation approaches, flavin-containing monooxygenases (FMOs) encoded by six tandem-repeat genes in the A. sesquipedale genome are identified as catalyzing the formation of oximes present. Further in vitro and in vivo assays confirm the function of FMOs in the oxime biosynthesis. We designate these FMOs as Orchid Oxime Synthases 1-6. The evolutionary aspects related to the CYP79 gene losses and neofunctionalization of FMO-catalyzed biosynthesis of oximes in Darwin's orchid provide new insights into the convergent evolution of biosynthetic pathways.PMID:39702965 | DOI:10.1016/j.molp.2024.12.010

Magn Reson Chem. 2024 Dec 19. doi: 10.1002/mrc.5504. Online ahead of print.ABSTRACTCatharanthus roseus, also known as Madagascar periwinkle, is a perennial plant renowned for its extensive pharmacological properties. It produces vital chemotherapeutic compounds, including vinblastine and vincristine, and exhibits anti-inflammatory, antidiabetic, and antioxidant activities. In this study, we utilized a range of two-dimensional (2D) nuclear magnetic resonance (NMR) techniques, such as 1H-1H correlation spectroscopy (COSY), 1H-1H J-resolved NMR, and 1H-13C heteronuclear single quantum coherence (HSQC) sensitivity-enhanced NMR spectroscopy, to identify key metabolites in C. roseus leaf extracts. Given the presence of numerous metabolites with closely spaced multiplet resonances, the 1H NMR spectra often exhibit significant signal overlap, making metabolite identification difficult or even impossible. However, the use of 2D NMR techniques effectively overcame this challenge, allowing for the precise identification of important alkaloids, such as vindoline, vinblastine, serpentine, and ajmalicine, along with essential metabolites like organic acids, amino acids, and carbohydrates. The extract contained a variety of bioactive compounds, including organic acids crucial for the tricarboxylic acid (TCA) cycle, branched-chain amino acids vital for metabolic functions, and alkaloids with substantial therapeutic potential. This comprehensive study underscores the continued significance of C. roseus in both traditional and modern medicine, emphasizing its intricate metabolic network and its potential in the development of novel therapeutics.PMID:39702899 | DOI:10.1002/mrc.5504

Metabolomics. 2024 Dec 19;21(1):11. doi: 10.1007/s11306-024-02209-9.ABSTRACTINTRODUCTION: Metabolic disorders are a global health concern, necessitating the development of drugs with fewer side effects and more efficacy. Traditional Indian medicine uses Tinospora cordifolia and Tinospora sinensis, but their metabolite fingerprints and impact on geographical location remains unknown.OBJECTIVE: The present study aimed to identify metabolite fingerprints from T. cordifolia and T. sinensis species from different geographic locations and also to identify potential quality markers for treating metabolic disorders.METHODS: Non-targeted metabolite fingerprinting of T. cordifolia and T. sinensis was performed using HPLC-QTOF-MS/MS analysis. Network pharmacology, molecular docking and molecular dynamics simulation analysis were performed to identify potential quality markers, hub targets, and key pathways associated with metabolic disorders.RESULTS: In this study, six potential marker compounds and twenty-five differential compounds were identified between T. cordifolia and T. sinensis. Based on geography, five and one metabolite marker compounds were identified in T. cordifolia and T. sinensis respectively. Network pharmacology, molecular docking, and molecular dynamics simulation analysis revealed trans piceid, crustecdysone in T. cordifolia, and gallic acid in T. sinensis as potential quality markers against metabolic disorder related hub targets.CONCLUSION: Integration of non-targeted metabolomics and network pharmacology approach deciphers the pharmacological mechanism of action in terms of identifying potential quality markers from Tinospora species that can be used against metabolic disorders. However, further research is required to validate these findings in in vitro and in vivo studies for better assertion.PMID:39702870 | DOI:10.1007/s11306-024-02209-9

Eye (Lond). 2024 Dec 19. doi: 10.1038/s41433-024-03517-z. Online ahead of print.ABSTRACTThe human microbiome has progressively been recognised for its role in various disease processes. In ophthalmology, complex interactions between the gut and distinct ocular microbiota within each structure and microenvironment of the eye has advanced our knowledge on the multi-directional relationships of these ecosystems. Increasingly, studies have shown that modulation of the microbiome can be achieved through faecal microbiota transplantation and synbiotics producing favourable outcomes for ophthalmic diseases. As ophthalmologists, we are obliged to educate our patients on measures to cultivate a healthy gut microbiome through a range of holistic measures. Further integrative studies combining microbial metagenomics, metatranscriptomics and metabolomics are necessary to fully characterise the human microbiome and enable targeted therapeutic interventions.PMID:39702789 | DOI:10.1038/s41433-024-03517-z

Appl Microbiol Biotechnol. 2024 Dec 19;108(1):538. doi: 10.1007/s00253-024-13384-z.ABSTRACTMetabolomics is a cutting-edge omics technology that identifies metabolites in organisms and their environments and tracks their fluctuations. This field has been extensively utilized to elucidate previously unknown metabolic pathways and to identify the underlying causes of metabolic changes, given its direct association with phenotypic alterations. However, metabolomics inherently has limitations that can lead to false positives and false negatives. First, most metabolites function as intermediates in multiple biochemical reactions, making it challenging to pinpoint which specific reaction is responsible for the observed changes in metabolite levels. Consequently, metabolic processes that are anticipated to vary with metabolite concentrations may not exhibit significant changes, generating false positives. Second, the range of metabolites identified is contingent upon the analytical conditions employed. Until now, no analytical instrument or protocol has been developed that can capture all metabolites simultaneously. Therefore, some metabolites are changed but are not detected, generating false negatives. In this review, we offer a novel and systematic assessment of the limitations of omics technologies and propose-specific strategies to minimize false positives and false negatives through multi-omics approaches. Additionally, we provide examples of multi-omics applications in microbial metabolic engineering and host-microbiome interactions, helping other researchers gain a better understanding of these strategies. KEY POINTS: • Metabolomics identifies metabolic shifts but has inherent false positive/negatives. • Multi-omics approaches help overcome metabolomics' inherent limitations.PMID:39702677 | DOI:10.1007/s00253-024-13384-z