PubMed

Nat Protoc. 2024 May 20. doi: 10.1038/s41596-024-00985-1. Online ahead of print.ABSTRACTOncolytic viruses (OVs) represent a novel class of cancer immunotherapy agents that preferentially infect and kill cancer cells and promote protective antitumor immunity. Furthermore, OVs can be used in combination with established or upcoming immunotherapeutic agents, especially immune checkpoint inhibitors, to efficiently target a wide range of malignancies. The development of OV-based therapy involves three major steps before clinical evaluation: design, production and preclinical testing. OVs can be designed as natural or engineered strains and subsequently selected for their ability to kill a broad spectrum of cancer cells rather than normal, healthy cells. OV selection is further influenced by multiple factors, such as the availability of a specific viral platform, cancer cell permissivity, the need for genetic engineering to render the virus non-pathogenic and/or more effective and logistical considerations around the use of OVs within the laboratory or clinical setting. Selected OVs are then produced and tested for their anticancer potential by using syngeneic, xenograft or humanized preclinical models wherein immunocompromised and immunocompetent setups are used to elucidate their direct oncolytic ability as well as indirect immunotherapeutic potential in vivo. Finally, OVs demonstrating the desired anticancer potential progress toward translation in patients with cancer. This tutorial provides guidelines for the design, production and preclinical testing of OVs, emphasizing considerations specific to OV technology that determine their clinical utility as cancer immunotherapy agents.PMID:38769145 | DOI:10.1038/s41596-024-00985-1

Nat Protoc. 2024 May 20. doi: 10.1038/s41596-024-00996-y. Online ahead of print.ABSTRACTUntargeted mass spectrometry (MS) experiments produce complex, multidimensional data that are practically impossible to investigate manually. For this reason, computational pipelines are needed to extract relevant information from raw spectral data and convert it into a more comprehensible format. Depending on the sample type and/or goal of the study, a variety of MS platforms can be used for such analysis. MZmine is an open-source software for the processing of raw spectral data generated by different MS platforms. Examples include liquid chromatography-MS, gas chromatography-MS and MS-imaging. These data might typically be associated with various applications including metabolomics and lipidomics. Moreover, the third version of the software, described herein, supports the processing of ion mobility spectrometry (IMS) data. The present protocol provides three distinct procedures to perform feature detection and annotation of untargeted MS data produced by different instrumental setups: liquid chromatography-(IMS-)MS, gas chromatography-MS and (IMS-)MS imaging. For training purposes, example datasets are provided together with configuration batch files (i.e., list of processing steps and parameters) to allow new users to easily replicate the described workflows. Depending on the number of data files and available computing resources, we anticipate this to take between 2 and 24 h for new MZmine users and nonexperts. Within each procedure, we provide a detailed description for all processing parameters together with instructions/recommendations for their optimization. The main generated outputs are represented by aligned feature tables and fragmentation spectra lists that can be used by other third-party tools for further downstream analysis.PMID:38769143 | DOI:10.1038/s41596-024-00996-y

Sci Rep. 2024 May 20;14(1):11510. doi: 10.1038/s41598-024-61680-5.ABSTRACTTextile waste contains both natural fibres such as cotton and bamboo viscose, and synthetic fibres such as elastane and polyester. As a complex mixture, textiles present a challenging pollution issue as breakdown in landfill results in microplastics entering water and soil environments, and incineration results in particulate air pollution. Here the use of edible fungi as bioremediation agents of waste textiles is described for the first time. Three species of filamentous fungi were shown to colonise and grow on mixed fibre textile waste (underpants made from 28% cotton: 68% bamboo viscose: 4% elastane). All three fungi were able to metabolise the common textile dye Reactive Black 5 to some extent. The metabolome was captured to elucidate the dye remediation pathway utilized and to characterise the volatiles released during bioremediation with a view to assessing the safety profile of this process for future industrial applications. The results suggest that edible fungi may be cultivated on textiles, and that some interesting and useful compounds may be produced in the process. This has great biotechnological potential. No mushrooms were produced in this study, suggesting that further work will be needed to optimise conditions for crop production from waste textiles.PMID:38769087 | DOI:10.1038/s41598-024-61680-5

FEBS Open Bio. 2024 May 20. doi: 10.1002/2211-5463.13814. Online ahead of print.ABSTRACTAlzheimer's disease (AD) is an increasingly important public health concern due to the increasing proportion of older individuals within the general population. The impairment of processes responsible for adequate brain energy supply primarily determines the early features of the aging process. Restricting brain energy supply results in brain hypometabolism prior to clinical symptoms and is anatomically and functionally associated with cognitive impairment. The present study investigated changes in metabolic profiles induced by intracerebroventricular-streptozotocin (ICV-STZ) in an AD-like animal model. To this end, male Wistar rats received a single injection of STZ (3 mg·kg-1) by ICV (2.5 μL into each ventricle for 5 min on each side). In the second week after receiving ICV-STZ, rats were tested for cognitive performance using the Morris Water Maze test and subsequently prepared for positron emission tomography (PET) to confirm AD-like symptoms. Tandem Mass Spectrometry (MS/MS) analysis was used to detect amino acid changes in cerebrospinal fluid (CFS) samples. Our metabolomics study revealed a reduction in the concentrations of various amino acids (alanine, arginine, aspartic acid, glutamic acid, glycine, isoleucine, methionine, phenylalanine, proline, serine, threonine, tryptophane, tyrosine, and valine) in CSF of ICV-STZ-treated animals as compared to controls rats. The results of the current study indicate amino acid levels could potentially be considered targets of nutritional and/or pharmacological interventions to interfere with AD progression.PMID:38769074 | DOI:10.1002/2211-5463.13814

PLoS One. 2024 May 20;19(5):e0303189. doi: 10.1371/journal.pone.0303189. eCollection 2024.ABSTRACTOBJECTIVES: To establish a rat model that accurately replicates the clinical characteristics of male infertility (MI) with Liver Depression and Kidney Deficiency (LD & KD) and investigate the pathogenesis.METHODS: After subjecting the rats to chronic restraint stress (CRS) and adenine treatment, a series of tests were conducted, including ethological assessments, evaluations of reproductive characteristics, measurements of biochemical parameters, histopathological examinations, and analyses of urinary metabolites. Additionally, bioinformatics predictions were performed for comprehensive analysis.RESULTS: Compared to the control, the model exhibited significant manifestations of MI with LD & KD, including reduced responsiveness, diminished frequency of capturing estrous female rats, and absence of mounting behavior. Additionally, the kidney coefficient increased markedly, while the coefficients of the testis and epididymis decreased significantly. Sperm counts and viabilities decreased notably, accompanied by an increase in sperm abnormalities. Dysregulation of reproductive hormone levels in the serum was observed, accompanied by an upregulation of proinflammatory cytokines expressions in the liver and kidney, as well as exacerbated oxidative stress in the penile corpus cavernosum and testis. The seminiferous tubules in the testis exhibited a loose arrangement, loss of germ cells, and infiltration of inflammatory cells. Furthermore, utilizing urinary metabolomics and bioinformatics analysis, 5 key biomarkers and 2 crucial targets most closely linked to MI were revealed.CONCLUSION: The study successfully established a clinically relevant animal model of MI with LD & KD. It elucidates the pathogenesis of the condition, identifies key biomarkers and targets, and provides a robust scientific foundation for the prediction, diagnosis, and treatment of MI with LD & KD.PMID:38768165 | DOI:10.1371/journal.pone.0303189

Med Sci Sports Exerc. 2024 May 15. doi: 10.1249/MSS.0000000000003483. Online ahead of print.ABSTRACTINTRODUCTION: The study aimed to investigate to what extent acute endurance exercise, especially eccentric exercise and cardiorespiratory fitness affect the metabolic profile of CD4+ cells.METHODS: 15 male, healthy adults aged between 20 and 33 years with a maximal oxygen uptake (VO2max) between 44 and 63 ml/kg/min performed a downhill run (DR) and a level run (LR) for 45 minutes at 70% of their VO2max on a treadmill in a cross-over design. Blood samples were taken before (T0), directly after (T1), 3 hours after (T3), and 24 hours (T24) after each exercise for analyzing leukocyte numbers and cytokine levels. Isolated CD4+ cells were incubated for 4 hours in autologous resting versus 3 hours after exercise serum (T3 DR and T3 LR), and subsequently, cellular respiration, transcriptomic, and metabolomics profiles were measured.RESULTS: The systemic immune inflammation index increased significantly after DR and LR at T1 and T3 (p < .001). In contrast, the transcriptomic and metabolic profile of CD4+ cells showed no significant alterations after incubation in T3 exercise serum. However, cardiorespiratory fitness positively correlated with the maximal mitochondrial respiration in CD4+ cells after incubation with T3 LR serum (r = .617, p = .033) and with gene expression of oxidative phosphorylation and levels of different metabolites. Similarly, VO2max was associated with an anti-inflammatory profile on RNA level. Lower lactate, methylmalonic acid, and D-gluconic acid levels were found in CD4+ cells of participants with a high VO2max (p < .001).CONCLUSIONS: Acute exercise leads to a mild pro-inflammatory milieu with only small changes in the metabolic homeostasis of CD4+ cells. High cardiorespiratory fitness is associated with a metabolic shift to oxidative phosphorylation in CD4+ cells. Functional relevance of this metabolic shift needs to be further investigated.PMID:38768035 | DOI:10.1249/MSS.0000000000003483

J Tradit Chin Med. 2024 Jun;44(3):515-523. doi: 10.19852/j.cnki.jtcm.20240423.006.ABSTRACTOBJECTIVE: To explore the material basis of the difference of efficacy of Dahuang (Radix Et Rhizoma Rhei Palmati)-Taoren (Semen Persicae) (DT) drugs with different proportions.METHODS: Samples of different ratios of Dahuang (Radix et Rhizoma Rhei Palnati, DH) to Taoren (Semen Persicae, TR) (Group A 1:1, B 2:3, C 3:2) were analyzed based on gas chromatography time-of-flight mass spectrometry untargeted metabolomics technique.RESULTS: A total of 240 primary metabolites were detected. Forty-one differential metabolites involved nine differential metabolic pathways, of which four were closely related to the efficacy of DT in the treatment of heat and blood stasis syndrome. These pathways included the biosynthesis of amino acid (phenylalanine tyrosine and tryptophan), flavonoids, unsaturated fatty acids, and the glycolysis/glycogenesis pathway.CONCLUSION: There are significant differences in the efficacy of different ratios of DT drugs, and their optimal ratio for the treatment of heat and blood stasis syndrome should be 1:1.PMID:38767635 | DOI:10.19852/j.cnki.jtcm.20240423.006

Cancer Res Commun. 2024 May 20. doi: 10.1158/2767-9764.CRC-24-0138. Online ahead of print.ABSTRACTAcute graft-versus-host disease (aGVHD) is a major complication of allogeneic hematopoietic cell transplantation (alloHCT) associated with gut microbiota disruptions. However, whether therapeutic microbiota modulation prevents aGVHD is unknown. We conducted a randomized, placebo-controlled trial of third-party fecal microbiota transplantation (FMT) administered at the peak of microbiota injury in 100 patients with acute myeloid leukemia receiving induction chemotherapy and alloHCT recipients. Despite improvements in microbiome diversity, expansion of commensals, and shrinkage of potential pathogens, aGVHD occurred more frequently after FMT than placebo. Although this unexpected finding could be explained by clinical differences between the two arms, we asked whether a microbiota explanation might be also present. To this end, we performed multi-omics analysis of pre- and post-intervention gut microbiome and serum metabolome. We found that post-intervention expansion of Faecalibacterium, a commensal genus with gut-protective and anti-inflammatory properties under homeostatic conditions, predicted a higher risk for aGVHD. Faecalibacterium expansion occurred predominantly after FMT and was due to engraftment of unique donor taxa, suggesting that donor Faecalibacterium-derived antigens might have stimulated allogeneic immune cells. Faecalibacterium and ursodeoxycholic acid (an anti-inflammatory secondary bile acid) were negatively correlated, offering an alternative mechanistic explanation. In conclusion, we demonstrate context dependence of microbiota effects where a normally beneficial bacteria may become detrimental in disease. While FMT is a broad, community-level intervention, it may need precision engineering in ecologically complex settings where multiple perturbations (e.g. antibiotics, intestinal damage, alloimmunity) are concurrently in effect.PMID:38767452 | DOI:10.1158/2767-9764.CRC-24-0138

mSystems. 2024 May 20:e0004824. doi: 10.1128/msystems.00048-24. Online ahead of print.ABSTRACTProbiotics and synbiotics have been intensively used in animal husbandry due to their advantageous roles in animals' health. However, there is a paucity of research on probiotic and synbiotic supplementation from maternal gestation to the postnatal growing phases of offspring piglets. Thus, we assessed the effects of dietary supplementation of these two additives to sows and offspring piglets on skeletal muscle and body metabolism, colonic microbiota composition, and metabolite profiles of offspring piglets. Pregnant Bama mini-pigs and their offspring piglets (after weaning) were fed either a basal diet or a basal diet supplemented with antibiotics, probiotics, or synbiotics. At 65, 95, and 125 days old, eight pigs per group were euthanized and sampled for analyses. Probiotics increased the intramuscular fat content in the psoas major muscle (PMM) at 95 days old, polyunsaturated fatty acid (PUFA) and n-3 PUFA levels in the longissimus dorsi muscle (LDM) at 65 days old, C16:1 level in the LDM at 125 days old, and upregulated ATGL, CPT-1, and HSL expressions in the PMM at 65 days old. Synbiotics increased the plasma HDL-C level at 65 days old and TC level at 65 and 125 days old and upregulated the CPT-1 expression in the PMM at 125 days old. In addition, probiotics and synbiotics increased the plasma levels of HDL-C at 65 days old, CHE at 95 days old, and LDL-C at 125 days old, while decreasing the C18:1n9t level in the PMM at 65 days old and the plasma levels of GLU, LDH, and TG at 95 days old. Microbiome analysis showed that probiotic and synbiotic supplementation increased colonic Actinobacteria, Firmicutes, Verrucomicrobia, Faecalibacterium, Pseudobutyrivibrio, and Turicibacter abundances. However, antibiotic supplementation decreased colonic Actinobacteria, Bacteroidetes, Prevotella, and Unclassified_Lachnospiraceae abundances. Furthermore, probiotic and synbiotic supplementation was associated with alterations in 8, 7, and 10 differential metabolites at three different age stages. Both microbiome and metabolome analyses showed that the differential metabolic pathways were associated with carbohydrate, amino acid, and lipid metabolism. However, antibiotic supplementation increased the C18:1n9t level in the PMM at 65 days old and xenobiotic biodegradation and metabolism at 125 days old. In conclusion, sow-offspring's diets supplemented with these two additives showed conducive effects on meat flavor, nutritional composition of skeletal muscles, and body metabolism, which may be associated with the reshaping of colonic microbiota and metabolites. However, antibiotic supplementation has negative effects on colonic microbiota composition and fatty acid composition in the PMM.IMPORTANCE: The integral sow-offspring probiotic and synbiotic supplementation improves the meat flavor and the fatty acid composition of the LDM to some extent. Sow-offspring probiotic and synbiotic supplementation increases the colonic beneficial bacteria (including Firmicutes, Verrucomicrobia, Actinobacteria, Faecalibacterium, Turicibacter, and Pseudobutyrivibrio) and alters the colonic metabolite profiles, such as guanidoacetic acid, beta-sitosterol, inosine, cellobiose, indole, and polyamine. Antibiotic supplementation in sow-offspring's diets decreases several beneficial bacteria (including Bacteroidetes, Actinobacteria, Unclassified_Lachnospiraceae, and Prevotella) and has a favorable effect on improving the fatty acid composition of the LDM to some extent, while presenting the opposite effect on the PMM.PMID:38767377 | DOI:10.1128/msystems.00048-24

FEBS J. 2024 May 20. doi: 10.1111/febs.17160. Online ahead of print.ABSTRACTA group of bacterial proteases, the Pro-Pro endopeptidases (PPEPs), possess the unique ability to hydrolyze proline-proline bonds in proteins. Since a protease's function is largely determined by its substrate specificity, methods that can extensively characterize substrate specificity are valuable tools for protease research. Previously, we achieved an in-depth characterization of PPEP prime-side specificity. However, PPEP specificity is also determined by the non-prime-side residues in the substrate. To gain a more complete insight into the determinants of PPEP specificity, we characterized the non-prime- and prime-side specificity of various PPEPs using a combination of synthetic combinatorial peptide libraries and mass spectrometry. With this approach, we deepened our understanding of the P3-P3' specificities of PPEP-1 and PPEP-2, while identifying the endogenous substrate of PPEP-2 as the most optimal substrate in our library data. Furthermore, by employing the library approach, we investigated the altered specificity of mutants of PPEP-1 and PPEP-2. Additionally, we characterized a novel PPEP from Anoxybacillus tepidamans, which we termed PPEP-4. Based on structural comparisons, we hypothesized that PPEP-4 displays a PPEP-1-like prime-side specificity, which was substantiated by the experimental data. Intriguingly, another putative PPEP from Clostridioides difficile, CD1597, did not display Pro-Pro endoproteolytic activity. Collectively, we characterized PPEP specificity in detail using our robust peptide library method and, together with additional structural information, provide more insight into the intricate mechanisms that govern protease specificity.PMID:38767318 | DOI:10.1111/febs.17160

Genet Med. 2024 May 16:101166. doi: 10.1016/j.gim.2024.101166. Online ahead of print.ABSTRACTPURPOSE: The function of FAM177A1 and its relationship to human disease is largely unknown. Recent studies have demonstrated FAM177A1 to be a critical immune-associated gene. One previous case study has linked FAM177A1 to a neurodevelopmental disorder in four siblings.METHODS: We identified five individuals from three unrelated families with biallelic variants in FAM177A1. The physiological function of FAM177A1 was studied in a zebrafish model organism and human cell lines with loss-of-function variants similar to the affected cohort.RESULTS: These individuals share a characteristic phenotype defined by macrocephaly, global developmental delay, intellectual disability, seizures, behavioral abnormalities, hypotonia, and gait disturbance. We show that FAM177A1 localizes to the Golgi complex in mammalian and zebrafish cells. Intersection of the RNA-seq and metabolomic datasets from FAM177A1-deficient human fibroblasts and whole zebrafish larvae demonstrated dysregulation of pathways associated with apoptosis, inflammation, and negative regulation of cell proliferation.CONCLUSION: Our data sheds light on the emerging function of FAM177A1 and defines FAM177A1-related neurodevelopmental disorder as a new clinical entity.PMID:38767059 | DOI:10.1016/j.gim.2024.101166

Pediatr Transplant. 2024 Jun;28(4):e14785. doi: 10.1111/petr.14785.ABSTRACTBACKGROUND: Long-term outcomes in pediatric kidney transplantation remain suboptimal, largely related to chronic rejection. Creatinine is a late marker of renal injury, and more sensitive, early markers of allograft injury are an active area of current research.METHODS: This is an educational review summarizing existing strategies for monitoring for rejection in kidney transplant recipients.RESULTS: We summarize supporting currently available clinical tests, including surveillance biopsy, donor specific antibodies, and donor-derived cell free DNA, as well as the potential limitations of these studies. In addition, we review the current avenues of active research, including transcriptomics, proteomics, metabolomics, and torque tenovirus levels.CONCLUSION: Advancing the use of noninvasive immune monitoring will depend on well-designed multicenter trials that include patients with stable graft function, include biopsy results on all patients, and can demonstrate both association with a patient-relevant clinical endpoint such as graft survival or change in glomerular filtration rate and a potential timepoint for intervention.PMID:38766986 | DOI:10.1111/petr.14785

J Extracell Vesicles. 2024 May;13(5):e12447. doi: 10.1002/jev2.12447.ABSTRACTThe continuous emergence of multidrug-resistant bacterial pathogens poses a major global healthcare challenge, with Klebsiella pneumoniae being a prominent threat. We conducted a comprehensive study on K. pneumoniae's antibiotic resistance mechanisms, focusing on outer membrane vesicles (OMVs) and polymyxin, a last-resort antibiotic. Our research demonstrates that OMVs protect bacteria from polymyxins. OMVs derived from Polymyxin B (PB)-stressed K. pneumoniae exhibited heightened protective efficacy due to increased vesiculation, compared to OMVs from unstressed Klebsiella. OMVs also shield bacteria from different bacterial families. This was validated ex vivo and in vivo using precision cut lung slices (PCLS) and Galleria mellonella. In all models, OMVs protected K. pneumoniae from PB and reduced the associated stress response on protein level. We observed significant changes in the lipid composition of OMVs upon PB treatment, affecting their binding capacity to PB. The altered binding capacity of single OMVs from PB stressed K. pneumoniae could be linked to a reduction in the lipid A amount of their released vesicles. Although the amount of lipid A per vesicle is reduced, the overall increase in the number of vesicles results in an increased protection because the sum of lipid A and therefore PB binding sites have increased. This unravels the mechanism of the altered PB protective efficacy of OMVs from PB stressed K. pneumoniae compared to control OMVs. The lipid A-dependent protective effect against PB was confirmed in vitro using artificial vesicles. Moreover, artificial vesicles successfully protected Klebsiella from PB ex vivo and in vivo. The findings indicate that OMVs act as protective shields for bacteria by binding to polymyxins, effectively serving as decoys and preventing antibiotic interaction with the cell surface. Our findings provide valuable insights into the mechanisms underlying antibiotic cross-protection and offer potential avenues for the development of novel therapeutic interventions to address the escalating threat of multidrug-resistant bacterial infections.PMID:38766978 | DOI:10.1002/jev2.12447

Eur Rev Med Pharmacol Sci. 2024 May;28(9):3289. doi: 10.26355/eurrev_202405_36194.ABSTRACTThe article "Metabolomic profiling of amino acid alterations in anorexia nervosa: implications for appetite regulation and therapeutic strategies", by K. Donato, K. Dhuli, A. Macchia, M.C. Medori, C. Micheletti, G. Bonetti, M.R. Ceccarini, T. Beccari, P. Chiurazzi, S. Cristoni, V. Benfatti, L. Dalla Ragione, M. Bertelli, published in Eur Rev Med Pharmacol Sci 2023; 27 (6 Suppl): 64-76-DOI: 10.26355/eurrev_202312_34691-PMID: 38112949 has been retracted by the Editor in Chief for the following reasons. Following some concerns raised on PubPeer, the Editor in Chief has started an investigation to assess the validity of the results. The outcome of the investigation revealed that the manuscript presented major flaws in the following: - Issues with ethical approval - Undeclared conflict of interest Consequently, the Editor in Chief mistrusts the results presented and has decided to retract the article. The authors disagree with this retraction. This article has been retracted. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/34691.PMID:38766780 | DOI:10.26355/eurrev_202405_36194

Exposome. 2023;3(1):osad008. doi: 10.1093/exposome/osad008. Epub 2023 Nov 23.ABSTRACTThe exposome refers to all of the internal and external life-long exposures that an individual experiences. These exposures, either acute or chronic, are associated with changes in metabolism that will positively or negatively influence the health and well-being of individuals. Nutrients and other dietary compounds modulate similar biochemical processes and have the potential in some cases to counteract the negative effects of exposures or enhance their beneficial effects. We present herein the concept of Nutritional Pharmacology/Toxicology which uses high-information metabolomics workflows to identify metabolic targets associated with exposures. Using this information, nutritional interventions can be designed toward those targets to mitigate adverse effects or enhance positive effects. We also discuss the potential for this approach in precision nutrition where nutrients/diet can be used to target gene-environment interactions and other subpopulation characteristics. Deriving these "nutrient cocktails" presents an opportunity to modify the effects of exposures for more beneficial outcomes in public health.PMID:38766521 | PMC:PMC11101153 | DOI:10.1093/exposome/osad008

Front Plant Sci. 2024 May 3;15:1393438. doi: 10.3389/fpls.2024.1393438. eCollection 2024.ABSTRACTPeanuts (Arachis hypogaea) are an essential oilseed crop known for their unique developmental process, characterized by aerial flowering followed by subterranean fruit development. This crop is polyploid, consisting of A and B subgenomes, which complicates its genetic analysis. The advent and progression of omics technologies-encompassing genomics, transcriptomics, proteomics, epigenomics, and metabolomics-have significantly advanced our understanding of peanut biology, particularly in the context of seed development and the regulation of seed-associated traits. Following the completion of the peanut reference genome, research has utilized omics data to elucidate the quantitative trait loci (QTL) associated with seed weight, oil content, protein content, fatty acid composition, sucrose content, and seed coat color as well as the regulatory mechanisms governing seed development. This review aims to summarize the advancements in peanut seed development regulation and trait analysis based on reference genome-guided omics studies. It provides an overview of the significant progress made in understanding the molecular basis of peanut seed development, offering insights into the complex genetic and epigenetic mechanisms that influence key agronomic traits. These studies highlight the significance of omics data in profoundly elucidating the regulatory mechanisms of peanut seed development. Furthermore, they lay a foundational basis for future research on trait-related functional genes, highlighting the pivotal role of comprehensive genomic analysis in advancing our understanding of plant biology.PMID:38766472 | PMC:PMC11099219 | DOI:10.3389/fpls.2024.1393438

Front Plant Sci. 2024 May 3;15:1364631. doi: 10.3389/fpls.2024.1364631. eCollection 2024.ABSTRACTINTRODUCTION: Watermelon is an annual vine of the family Cucurbitaceae. Watermelon plants produce a fruit that people love and have important nutritional and economic value. With global warming and deterioration of the ecological environment, abiotic stresses, including drought, have become important factors that impact the yield and quality of watermelon plants. Previous research on watermelon drought resistance has included analyzing homologous genes based on known drought-responsive genes and pathways in other species.METHODS: However, identifying key pathways and genes involved in watermelon drought resistance through high-throughput omics methods is particularly important. In this study, RNA-seq and metabolomic analysis were performed on watermelon plants at five time points (0 h, 1 h, 6 h, 12 h and 24 h) before and after drought stress.RESULTS: Transcriptomic analysis revealed 7829 differentially expressed genes (DEGs) at the five time points. The DEGs were grouped into five clusters using the k-means clustering algorithm. The functional category for each cluster was annotated based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database; different clusters were associated with different time points after stress. A total of 949 metabolites were divided into 10 categories, with lipids and lipid-like molecules accounting for the most metabolites. Differential expression analysis revealed 22 differentially regulated metabolites (DRMs) among the five time points. Through joint analysis of RNA-seq and metabolome data, the 6-h period was identified as the critical period for watermelon drought resistance, and the starch and sucrose metabolism, plant hormone signal transduction and photosynthesis pathways were identified as important regulatory pathways involved in watermelon drought resistance. In addition, 15 candidate genes associated with watermelon drought resistance were identified through joint RNA-seq and metabolome analysis combined with weighted correlation network analysis (WGCNA). Four of these genes encode transcription factors, including bHLH (Cla97C03G068160), MYB (Cla97C01G002440), HSP (Cla97C02G033390) and GRF (Cla97C02G042620), one key gene in the ABA pathway, SnRK2-4 (Cla97C10G186750), and the GP-2 gene (Cla97C05G105810), which is involved in the starch and sucrose metabolism pathway.DISCUSSION: In summary, our study provides a theoretical basis for elucidating the molecular mechanisms underlying drought resistance in watermelon plants and provides new genetic resources for the study of drought resistance in this crop.PMID:38766468 | PMC:PMC11102048 | DOI:10.3389/fpls.2024.1364631

World J Diabetes. 2024 May 15;15(5):1021-1044. doi: 10.4239/wjd.v15.i5.1021.ABSTRACTBACKGROUND: Diabetes is a metabolic disease characterized by hyperglycemia, which has increased the global medical burden and is also the main cause of death in most countries.AIM: To understand the knowledge structure of global development status, research focus, and future trend of the relationship between diabetes and metabolomics in the past 20 years.METHODS: The articles about the relationship between diabetes and metabolomics in the Web of Science Core Collection were retrieved from 2002 to October 23, 2023, and the relevant information was analyzed using CiteSpace6.2.2R (CiteSpace), VOSviewer6.1.18 (VOSviewer), and Bibliometrix software under R language.RESULTS: A total of 3123 publications were included from 2002 to 2022. In the past two decades, the number of publications and citations in this field has continued to increase. The United States, China, Germany, the United Kingdom, and other relevant funds, institutions, and authors have significantly contributed to this field. Scientific Reports and PLoS One are the journals with the most publications and the most citations. Through keyword co-occurrence and cluster analysis, the closely related keywords are "insulin resistance", "risk", "obesity", "oxidative stress", "metabolomics", "metabolites" and "biomarkers". Keyword clustering included cardiovascular disease, gut microbiota, metabonomics, diabetic nephropathy, molecular docking, gestational diabetes mellitus, oxidative stress, and insulin resistance. Burst detection analysis of keyword depicted that "Gene", "microbiota", "validation", "kidney disease", "antioxidant activity", "untargeted metabolomics", "management", and "accumulation" are knowledge frontiers in recent years.CONCLUSION: The relationship between metabolomics and diabetes is receiving extensive attention. Diabetic nephropathy, diabetic cardiovascular disease, and kidney disease are key diseases for future research in this field. Gut microbiota, molecular docking, and untargeted metabolomics are key research directions in the future. Antioxidant activity, gene, validation, mass spectrometry, management, and accumulation are at the forefront of knowledge frontiers in this field.PMID:38766424 | PMC:PMC11099375 | DOI:10.4239/wjd.v15.i5.1021

Int J Ophthalmol. 2024 May 18;17(5):883-895. doi: 10.18240/ijo.2024.05.13. eCollection 2024.ABSTRACTAIM: To explore the correlation of gut microbiota and the metabolites with the progression of diabetic retinopathy (DR) and provide a novel strategy to elucidate the pathological mechanism of DR.METHODS: The fecal samples from 32 type 2 diabetes patients with proliferative retinopathy (PDR), 23 with non-proliferative retinopathy (NPDR), 27 without retinopathy (DM), and 29 from the sex-, age- and BMI- matched healthy controls (29 HC) were analyzed by 16S rDNA gene sequencing. Sixty fecal samples from PDR, DM, and HC groups were assayed by untargeted metabolomics. Fecal metabolites were measured using liquid chromatography-mass spectrometry (LC-MS) analysis. Associations between gut microbiota and fecal metabolites were analyzed.RESULTS: A cluster of 2 microbiome and 12 metabolites accompanied with the severity of DR, and the close correlation of the disease progression with PDR-related microbiome and metabolites were found. To be specific, the structure of gut microbiota differed in four groups. Diversity and richness of gut microbiota were significantly lower in PDR and NPDR groups, than those in DM and HC groups. A cluster of microbiome enriched in PDR group, including Pseudomonas, Ruminococcaceae-UCG-002, Ruminococcaceae-UCG-005, Christensenellaceae-R-7, was observed. Functional analysis showed that the glucose and nicotinate degradations were significantly higher in PDR group than those in HC group. Arginine, serine, ornithine, and arachidonic acid were significantly enriched in PDR group, while proline was enriched in HC group. Functional analysis illustrated that arginine biosynthesis, lysine degradation, histidine catabolism, central carbon catabolism in cancer, D-arginine and D-ornithine catabolism were elevated in PDR group. Correlation analysis revealed that Ruminococcaceae-UCG-002 and Christensenellaceae-R-7 were positively associated with L-arginine, ornithine levels in fecal samples.CONCLUSION: This study elaborates the different microbiota structure in the gut from four groups. The relative abundance of Ruminococcaceae-UCG-002 and Parabacteroides are associated with the severity of DR. Amino acid and fatty acid catabolism is especially disordered in PDR group. This may help provide a novel diagnostic parameter for DR, especially PDR.PMID:38766339 | PMC:PMC11074191 | DOI:10.18240/ijo.2024.05.13

bioRxiv [Preprint]. 2024 May 6:2024.05.06.592725. doi: 10.1101/2024.05.06.592725.ABSTRACTCampylobacter infections are a leading cause of bacterial-derived gastroenteritis worldwide with particularly profound impacts on pediatric patients in low-and-middle income countries. It remains unclear how Campylobacter impacts these hosts, though it is becoming increasingly evident that it is a multifactorial process that depends on the host immune response, the gastrointestinal microbiota, various bacterial factors, and host nutritional status. Since these factors likely vary between adult and pediatric patients in different regions of the world, it is important that studies define these attributes in well characterized clinical cohorts in diverse settings. In this study, we analyzed the fecal microbiota and the metabolomic and micronutrient profiles of asymptomatic and symptomatic pediatric patients in Colombia that were either infected or uninfected with Campylobacter during a case-controlled study on acute diarrheal disease. Here, we report that the microbiome of Campylobacter- infected children only changed in their abundance of Campylobacter spp. despite the inclusion of children with or without diarrhea. In addition to increased Campylobacter, computational models were used to identify fecal metabolites that were associated with Campylobacter infection and found that glucose-6-phosphate and homovanillic acid were the strongest predictors of infection in these pediatric patients, which suggest that colonocyte metabolism are impacted during infection. Despite changes to the fecal metabolome, the concentrations of intestinal minerals and trace elements were not significantly impacted by Campylobacter infection, but were elevated in uninfected children with diarrhea.IMPORTANCE: Gastrointestinal infection with pathogenic Campylobacter species has long been recognized as a significant cause of human morbidity. Recently, it has been observed that pediatric populations in low-and-middle income countries are uniquely impacted by these organisms in that infected children can be persistently colonized, develop enteric dysfunction, and exhibit reduced development and growth. While the association of Campylobacter species with these long-term effects continues to emerge, the impact of infection on the gastrointestinal environment of these children remains uncharacterized. To address this knowledge gap, our group leveraged clinical samples collected during a previous study on gastrointestinal infections in pediatric patients to examine the fecal microbiota, metabolome, and micronutrient profiles of those infected with Campylobacter species, and found that the metabolome was impacted in a way that suggests gastrointestinal cell metabolism is affected during infection, which is some of the first data indicating how gastrointestinal health in these patients may be affected.PMID:38766229 | PMC:PMC11100603 | DOI:10.1101/2024.05.06.592725