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At least 19 recordsLinked to original sources

PubMed2026

Genetically predicted lower FLT3L levels increase the risk of hypertrophic cardiomyopathy partly mediated by phosphate: Evidence from a 2-step Mendelian randomization analysis.

We performed a 2-step Mendelian randomization (MR) study to investigate the associations of Fms-related tyrosine kinase 3 ligand (FLT3L) and phosphate levels with the risk of hypertrophic cardiomyopathy (HCM). Genetic instruments for 75 circulating inflammatory factors were obtained from the NHGRI-EBI GWAS Catalog, while summary statistics for circulating phosphate and HCM were derived from the UK Biobank and FinnGen, respectively. Univariable MR analysis using the inverse-variance weighted method indicated that genetically predicted higher phosphate levels were associated with an increased risk of HCM (OR = 1.36, P = 4.82 × 10-2). Among the inflammatory markers, FLT3L emerged as a significant candidate and showed inverse associations with phosphate levels (β = -0.05, P = 1.70 × 10-9) and HCM (OR = 0.79, P = 4.10 × 10-2). Bidirectional MR analyses did not support a causal effect of phosphate on FLT3L. Mediation analysis suggested that phosphate levels accounted for an estimated 12.05% of the total effect of FLT3L on HCM. Genetic liability to lower FLT3L levels is associated with a higher risk of HCM, and this relationship may be partially mediated through circulating phosphate levels.

Humans↗

PubMed2026

The removal of iron and phosphate from culture medium by Rhodococcus ruber SiAl.

The microbial accumulation of heavy metals and phosphate is of interest for the bioremediation of polluted waters. In this work, we showed that at cultivation of the bacterium Rhodococcus ruber SiAl in the medium with 2.0 mM Fe³⁺ for stationary growth stage, up to 99% of the iron was associated with the biomass. Magnesium ion accumulation from the medium with 2 mM Mg²⁺ did not exceed 5% of the initial content. The cells did not remove manganese ions from the medium; moreover, the presence of MnSO4 inhibited growth. The cells of Rhodococcus ruber SiAl removed phosphate from the medium: 75, 20, and 10% of the initial phosphate content was removed during cultivation in the presence of 6 mM phosphate and 2 mM Fe³⁺, 2 mM Mg²⁺, or 2 mM Mn²⁺, respectively. In the genome of R. ruber SiAl, genes encoding proteins of the siderophore synthesis systems and phosphate transport systems were identified. The strain was the most efficient for iron accumulation, which suggests a promising application for the removal of phosphate and iron from polluted waters.

Rhodococcus ruber↗

PubMed2026

Plant genetic and root-associated microbial diversity modulate Lactuca sativa responsiveness to a soil inoculum under phosphate deficiency.

Microbial-based approaches offer a promising strategy to decrease the use of chemical fertilizers in agriculture. Among them, arbuscular mycorrhizal fungi (AMF), which extend root surface area and enhance phosphate uptake, and phosphate-solubilizing bacteria (PSB) are particularly relevant. However, their effectiveness depends strongly on plant genetic diversity. To identify genetic markers underlying plant responses to beneficial soil microbes, we studied a panel of 128 fully sequenced Lactuca sativa varieties under controlled phosphate-starvation conditions and treated with AMF and PSB. Lettuce genetic variation showed a strong effect on physiological and morphological responses to microbial inoculation. Genome-wide association studies identified specific genomic regions associated with changes in leaf phosphate content and shoot biomass following treatment. Beyond genetic factors, we observed shifts in fungal β-diversity and increased bacterial α-diversity associated with phenotypic variation. We also identified 44 amplicon sequence variants associated with agriculturally relevant traits. Among these, six bacterial strains were experimentally validated through in vitro and pot experiments for their effects on leaf phosphate concentration and shoot biomass. Overall, we highlighted key genetic, microbial, and physiological mechanisms that may enhance microbial treatments for improved plant phosphate management in lettuce.

16S and ITS metabarcoding↗

PubMed2025

Multiple clades of regulators contribute to bacterial phosphate homeostasis and pathogenesis.

Phosphate is both essential for life and toxic, necessitating the tight regulation of its acquisition. Based on Escherichia coli, most bacteria are thought to use a single accessory protein that monitors import to regulate phosphate homeostasis. This work reveals that most bacteria possess multiple distinct families of accessory regulators with each family regulating homeostasis in conjunction with a unique importer family. The antibiotic-resistant pathogen Staphylococcus aureus can obtain phosphate from divergent environments and possesses accessory-transporter pairs from all three identified groups. Investigations with S. aureus revealed that all three accessory proteins can regulate phosphate homeostasis, but that there is a hierarchy, which is dictated by the environment. Multiple accessory regulators are independently necessary for S. aureus to cause infection. Thus, microbes possess not one, but multiple distinct groups of accessory regulatory proteins and this diversity enables them to control phosphate homeostasis across environments, including those encountered during infection.

PhoPR↗

PubMed2024

The NRF2-CARM1 axis links glucose sensing to transcriptional and epigenetic regulation of the pentose phosphate pathway in gastric cancer.

Cancer cells autonomously alter metabolic pathways in response to dynamic nutrient conditions in the microenvironment to maintain cell survival and proliferation. A better understanding of these adaptive alterations may reveal the vulnerabilities of cancer cells. Here, we demonstrate that coactivator-associated arginine methyltransferase 1 (CARM1) is frequently overexpressed in gastric cancer and predicts poor prognosis of patients with this cancer. Gastric cancer cells sense a reduced extracellular glucose content, leading to activation of nuclear factor erythroid 2-related factor 2 (NRF2). Subsequently, NRF2 mediates the classic antioxidant pathway to eliminate the accumulation of reactive oxygen species induced by low glucose. We found that NRF2 binds to the CARM1 promoter, upregulating its expression and triggering CARM1-mediated hypermethylation of histone H3 methylated at R arginine 17 (H3R17me2) in the glucose-6-phosphate dehydrogenase gene body. The upregulation of this dehydrogenase, driven by the H3R17me2 modification, redirects glucose carbon flux toward the pentose phosphate pathway. This redirection contributes to nucleotide synthesis (yielding nucleotide precursors, such as ribose-5-phosphate) and redox homeostasis and ultimately facilitates cancer cell survival and growth. NRF2 or CARM1 knockdown results in decreased H3R17me2a accompanied by the reduction of glucose-6-phosphate dehydrogenase under low glucose conditions. Collectively, this study reveals a significant role of CARM1 in regulating the tumor metabolic switch and identifies CARM1 as a potential therapeutic target for gastric cancer treatment.

Stomach Neoplasms↗

PubMed2026

A ribozyme ligase that requires a 3' terminal phosphate on its RNA substrate.

Ribozymes likely played essential roles in catalyzing metabolic processes and facilitating genome replication in primordial RNA-based life. In vitro evolution has allowed us to expand the biochemical capabilities of RNA, especially new ribozyme chemistries. Here, we report the serendipitous discovery of ribozyme ligases that catalyze the attack of the 2'-hydroxyl group of an RNA substrate on its own 5'-triphosphate group, but only when the substrate possesses a 3'-phosphate vicinal to its nucleophilic 2'-hydroxyl group. The ligases' requirement for a 3'-phosphate group on its substrate resembles enzymatic mechanisms found in protein-based RNA repair pathways. We propose that ribozyme-catalyzed ligation of 3'-phosphorylated RNA could have provided pathways for RNA repair in primordial cells. We demonstrate that these ribozymes ligate specifically to 3'-phosphorylated RNA present in a heterogeneous mixture of cellular RNAs. We further show that these ribozymes can capture cleaved RNAs with 3'-phosphate and 2'-3'-cyclic phosphate termini, enabling us to selectively amplify the captured RNAs. These results demonstrate their potential utility as enrichment reagents for profiling RNA cleavage products in transcriptomics studies. Our findings not only report a new catalytic reactivity in RNA but also provide insights into ribozyme evolution, primordial RNA repair, and potential applications in RNA sequencing.

RNA, Catalytic↗

PubMed2026

The link between phosphate starvation-triggered anthocyanin biosynthesis and jasmonate-driven regulation in tomato.

Phosphate Starvation Response (PSR) in plants integrates inorganic phosphate (Pi) sensing with hormonal and metabolic reprogramming. Recent evidence supports a PSR-jasmonate (JA)-anthocyanin axis in which the PSR-associated PHOSPHATE STARVATION RESPONSE (PHR)/PHR-like-SYG1-PHO81-XPR1-inositol pyrophosphate 8 (PHR/PHL-SPX-InsP8) module gates transcriptional activation, while the core JA components JASMONATE ZIM-DOMAIN (JAZ) and MYELOCYTOMATOSIS 2 (MYC2) mediate hormone-induced activation of secondary metabolism. In Solanum lycopersicum, PHR/PHL transcription factors (TFs) serve as core PSR hubs, with expanded regulatory networks and InsP-associated control layers that tune SPX buffering and transcriptional output. Downstream, JA signaling and MYC2-dependent transcription interface with anthocyanin regulators, including key MYB and bHLH TFs that form the MYB-basic helix-loop-helix (bHLH)-WD40 repeat (MBW) complex, thereby regulating tissue capacity for pigmentation under Pi starvation (PiS). Anthocyanin-rich tomato cultivars such as 'Indigo Rose' exemplify how genetic configuration can enhance MBW responsiveness and potentiate pigment accumulation under PiS. Here, we collate recent advances linking PSR gating, JA response, and anthocyanin biosynthesis regulation in tomato, and propose a working model with testable predictions to accelerate causal validation, and enable breeding strategies targeting phosphorus use efficiency and nutritional quality.

Solanum lycopersicum↗

PubMed2025

The adjacent ATP-binding protein-encoding genes of the Enterococcus faecalis phosphate-specific transport (pst) locus have non-overlapping cellular functions.

UNLABELLED: The widely conserved pst-phoU operon encodes a low-velocity, high-affinity, ATP-dependent importer for inorganic phosphate (Pi). The pstB gene encodes the ATPase that powers the import of Pi into the cell. In some Firmicutes, including the gastrointestinal commensal and opportunistic pathogen Enterococcus faecalis, the pst-phoU locus contains adjacent pstB genes. In this work, we compared the functionality of E. faecalis pstB1 and pstB2. E. faecalis pstB1 and pstB2 share sequence similarities with verified PstB ATPases from Escherichia coli and Streptococcus pneumoniae and only share ~60% amino acid identity with each other. Deletion of pstB1 was associated with a growth defect in low Pi-containing chemically defined medium (CDM), reduced Pi uptake, and a moderate increase in alkaline phosphatase (AP) activity. Deletion of pstB2 fully inhibited growth in CDM regardless of inorganic phosphorus source but did not hinder growth in rich, undefined medium. The ΔpstB2 mutant also exhibited a significant increase in AP activity that was associated with extracellular Pi accumulation. Overexpression of pstB2 in the pstB1 mutant was sufficient to restore growth in low-Pi CDM, Pi uptake, and AP activity, but this was not recapitulated with overexpression of pstB1 in the ΔpstB2 mutant. Deletion of either pstB paralog increased expression of the tandem paralog, and overexpression of pstB2 in ΔpstB2 reduced pstB1 expression. These results suggest that the E. faecalis pstB2-encoded ATPase is required for Pi import, while the pstB1-encoded ATPase has an accessory role in Pi import that can be duplicated by the presence of excess PstB2. IMPORTANCE: Phosphate is critical for all microbial life. In many bacteria, inorganic phosphate (Pi) is imported by the high-affinity, low-velocity Pst-PhoU system. The pstB gene encodes the ATPase that powers Pi import. The pst-phoU operon in many Firmicutes, including the human commensal and opportunistic pathogen Enterococcus faecalis, contains adjacent pstB genes, pstB1 and pstB2. No studies on the relative biological contributions of tandem pstB paralogs in any microbe have been published. This genetic study indicates that E. faecalis pstB1 and pstB2 do not have equivalent functions. The pstB2 gene encodes an ATPase that is required for Pi import, while the ATPase encoded by pstB1 has an accessory role in Pi import that can be duplicated by the presence of excess PstB2.

Enterococcus faecalis↗

PubMed2025

Biosynthesis of Ribose-5-Phosphate-Metabolic Regulator of Escherichia coli Viability.

Biosynthesis of ribose-5-phosphate (R5P) underlies all biosynthetic processes associated with biomass growth. Actively dividing cells continuously require building blocks for genome replication, synthesis of ribosomes and other derivatives containing R5P as a carbohydrate backbone. The main source of R5P in the cell is the pentose phosphate pathway (PPP), which is an anabolic sensor designed to coordinate the level of pentose phosphates and reduced NADPH required for anabolic processes. This review is devoted to a comparative analysis of R5P biosynthesis pathways among different domains of microorganisms, the features of PPP regulation in bacterial cells depending on physiological conditions, as well as genetic modifications of PPP and their effect on cell viability. We emphasize that ribose metabolism is a factor in the consolidation of cellular homeostasis under conditions of intensive biomass growth and the discrepancy between the processes of ribose synthesis and consumption is marked by spontaneous cell death.

Escherichia coli↗

PubMed2026

Isolation and genomic characterization of Bacillus X32: a potent phosphate-solubilizing bacterium with growth-promoting effects on navel orange seedlings.

Phosphorus is an essential element for plant growth. However, in nature, most phosphorus exists in the form of insoluble compounds that plants cannot directly absorb, leading to phosphorus deficiency in agricultural systems. With increasing demand for economic crops such as citrus and the decline in soil fertility due to current management practices, there is a growing need for environmentally friendly fertilizers to improve and restore soil conditions. In this study, a highly efficient phosphate‑solubilizing strain X32 was isolated from the rhizosphere soil of Gannan navel oranges. Systematic genomic analysis identified it as a putative novel species within the genus Bacillus, showing the closest phylogenetic relationship to Bacillus spizizenii. However, both the average nucleotide identity (ANI = 93.18%) and digital DNA‑DNA hybridization (dDDH = 50.4%) values fell below the established thresholds for species delineation, indicating significant genomic differentiation. Whole‑genome sequencing further revealed that strain X32 harbors multiple functional genes potentially related to phosphorus metabolism, including inorganic phosphate‑solubilizing genes (e.g., gdh and gltA), phosphate transport genes (e.g., glpT, pstA, pstB, pstC), and phosphorus mineralization genes (e.g., phoA, phoD). Pot experiment results demonstrated that inoculation with strain X32 significantly promoted the growth of navel orange seedlings, as evidenced by marked increases in both aboveground and belowground fresh and dry weights, as well as plant height. Additionally, strain X32 significantly enhanced the activities of antioxidant enzymes (SOD, CAT, POD) and regulated the content of chlorophyll b in seedling leaves, these changes suggest that strain X32 may enhance stress resistance in plants and influence photosynthetic pigment composition, though direct measurements of photosynthetic performance are needed for confirmation. This study provides a theoretical basis for developing microbial fertilizers with efficient phosphorus solubilization and plant growth-promoting functions, which may help reduce dependence on phosphorus fertilizers and promote sustainable agricultural development.

Phosphates↗

PubMed2026

Phosphate backbone epitranscriptomics: Discovery of natural RNA phosphorothioates and their writer machinery.

Over 150 modifications expand the RNA alphabet, yet all known natural modifications occur on nucleobases or ribose sugars, with none identified on the phosphate backbone. In contrast, phosphorothioates (PSs), in which a non-bridging phosphate oxygen is replaced with sulfur, are central to RNA therapeutics but have never been reliably detected in natural RNAs. Here, we develop sequencing- and mass spectrometry-based approaches to quantitatively map RNA PSs at single-nucleotide resolution. Across diverse archaeal species, we identify stereospecific PS modifications at rRNA and tRNA hotspots, which are dynamically regulated by sulfur availability and temperature. We uncover a diverse enzyme family that selectively modifies tRNA/rRNA substrates and whose evolutionary presence/absence matches the distribution of PSs. Enzyme loss causes inviability or temperature sensitivity, and functional analyses reveal that tRNA PSs enhance tRNA stability. These findings establish the first natural RNA phosphate-backbone modification and its enzymatic machinery, providing a foundation for mechanistic and functional exploration.

RNA modifications↗

PubMed2026

The phosphate exporter XPR1 promotes gasdermin D-independent mature IL-1β secretion.

Interleukin (IL)-1β is a leaderless inflammatory cytokine that is not secreted via the classical endoplasmic reticulum-Golgi pathway. Instead, m(ature) IL-1β secretion is classically associated with pyroptosis, a caspase-dependent inflammatory cell death mediated by gasdermin D (GSDMD) pore formation at the plasma membrane. However, human monocytes can secrete mIL-1β in the absence of cell death, and the contribution of GSDMD in this secretory pathway remains poorly defined. Here, we distinguished two pathways for mIL-1β secretion in living human monocytic cells : a rapid, GSDMD-dependent pathway and a slower, GSDMD-independent pathway. Using a genome-wide CRISPR-Cas9 screen, we identified XPR1 (Xenotropic and Polytropic retrovirus Receptor 1) as a regulator of the GSDMD-independent pathway. XPR1, the only phosphate exporter identified in metazoans, has not previously been implicated in cytokine secretion. Genetic invalidation of XPR1 in GSDMD-deficient monocytic cells markedly reduced IL-1β secretion. We further showed that this regulatory function requires XPR1 surface expression and phosphate export activity. These findings reveal an unexpected link between phosphate homeostasis and non-lytic mIL-1β secretion, opening new opportunities to modulate IL-1β-driven inflammatory diseases.

IL-1β secretion↗

PubMed2024

Triphenyl Phosphate Alters Methyltransferase Expression and Induces Genome-Wide Aberrant DNA Methylation in Zebrafish Larvae.

Emerging environmental contaminants, organophosphate flame retardants (OPFRs), pose significant threats to ecosystems and human health. Despite numerous studies reporting the toxic effects of OPFRs, research on their epigenetic alterations remains limited. In this study, we investigated the effects of exposure to 2-ethylhexyl diphenyl phosphate (EHDPP), tricresyl phosphate (TMPP), and triphenyl phosphate (TPHP) on DNA methylation patterns during zebrafish embryonic development. We assessed general toxicity and morphological changes, measured global DNA methylation and hydroxymethylation levels, and evaluated DNA methyltransferase (DNMT) enzyme activity, as well as mRNA expression of DNMTs and ten-eleven translocation (TET) methylcytosine dioxygenase genes. Additionally, we analyzed genome-wide methylation patterns in zebrafish larvae using reduced-representation bisulfite sequencing. Our morphological assessment revealed no general toxicity, but a statistically significant yet subtle decrease in body length following exposure to TMPP and EHDPP, along with a reduction in head height after TPHP exposure, was observed. Eye diameter and head width were unaffected by any of the OPFRs. There were no significant changes in global DNA methylation levels in any exposure group, and TMPP showed no clear effect on DNMT expression. However, EHDPP significantly decreased only DNMT1 expression, while TPHP exposure reduced the expression of several DNMT orthologues and TETs in zebrafish larvae, leading to genome-wide aberrant DNA methylation. Differential methylation occurred primarily in introns (43%) and intergenic regions (37%), with 9% and 10% occurring in exons and promoter regions, respectively. Pathway enrichment analysis of differentially methylated region-associated genes indicated that TPHP exposure enhanced several biological and molecular functions corresponding to metabolism and neurological development. KEGG enrichment analysis further revealed TPHP-mediated potential effects on several signaling pathways including TGFβ, cytokine, and insulin signaling. This study identifies specific changes in DNA methylation in zebrafish larvae after TPHP exposure and brings novel insights into the epigenetic mode of action of TPHP.

Animals↗

PubMed2025

AFL1 is a phosphoinositide phosphate- and actin-binding protein.

At14a-Like 1 (AFL1) is highly induced during low water potential stress and remains at high levels during stress acclimation. AFL1, and the closely related At14a, are plant-specific proteins that have limited similarity to mammalian actin- and membrane-associated proteins. Previous research indicated that manipulation of AFL1 expression affects actin cytoskeleton dynamics and endocytic trafficking (as measured by uptake of membrane dye FM4-64). However, it has remained unclear whether this is a direct activity of AFL1 or an indirect effect. We found that AFL1 specifically bound actin filaments as well as the phosphoinositide phosphates (PIPs) phosphoinositide-3-monophosphate [PI(3)P], PI(5)P, and the diphosphate PI(3,5)P2 in co-sedimentation and PIP strip membrane assays, respectively. Interestingly, these binding activities were mediated by the same site within the C-terminal domain of AFL1. Mutation of a single amino acid in the AFL1 C-terminal domain was sufficient to disrupt both actin filament and PIP binding in vitro and to disrupt accumulation of the mutated protein in transgenic plants. We also found that the central hydrophobic region of AFL1 was required for AFL1 co-localization with actin filaments and plasma membrane. Mutation of AFL1 and At14a using genome editing confirmed that loss of these proteins reduced growth during low water potential stress and resulted in less extensive actin filament arrays and disrupted FM4-64 uptake. Together these observations indicate that AFL1 can directly participate in cytoskeleton organization and membrane dynamics via PIP and actin filament binding.

Arabidopsis↗

PubMed2026

Metabolic atlas of early human cortex reveals glycolytic remodeling and pentose phosphate pathway control of cell fate transitions.

Cortical development involves rapid progenitor expansion and cell diversification supported by tightly regulated metabolic programs, yet these programs remain largely uncharacterized in human development. Here, we generated a metabolic atlas of the early human cortex using primary tissue and stem cell-derived cortical organoids. We observed dynamic changes in core metabolic functions, including an unexpected increase in glycolysis and pentose phosphate pathway (PPP) activity during late neurogenesis. Manipulation of glucose availability in cortical organoids altered cell-type composition, increasing outer radial glia (oRG) and inhibitory neuron populations. Pharmacological and genetic inhibition of PPP enzymes recapitulated these cell fate changes. Ribose was sufficient to rescue radial glia (RG) gene expression changes, revert organoid cell-type composition, and restore levels of ATP and hypotaurine. These data identify a critical role for the PPP in modulating RG cell fate specification and generate a resource for future exploration of additional metabolic pathways in human cortical development.

cell fate↗

PubMed2026

The Pyridoxal-5'-Phosphate-Dependent Enzymes of Mycobacterium tuberculosis.

Enzymes that depend on the cofactor pyridoxal 5'-phosphate (PLP) catalyze a remarkable variety of biochemical reactions in all organisms. In particular, the genome of Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), encodes 45 bona fide PLP-dependent enzymes plus a few related proteins that presumably do not have enzymic function. The large majority of the 45 enzymes have been characterized in terms of catalytic activity and structure. Several of them have been shown to be central to the bacterium's survival and pathogenicity, while some of these enzymes are targets of an extant drug (d-cycloserine). Herein, the annotated catalog of the PLP-dependent enzymes in M. tuberculosis is presented and analyzed with three main goals in mind. The first will be to assess the specific aspects of mycobacterial metabolism that rely most on PLP-dependent enzymes. A second goal will be to signal those enzymes whose function is still uncertain and whose functional characterization may help to further understand the biology of M. tuberculosis. Finally, we will examine the potential and limitations of targeting the PLP-dependent enzymes for the development of new antimycobacterial drugs.

Mycobacterium tuberculosis↗

PubMed2026

Genome-wide Association Studies of the Pathogenic Sphingosine-1-Phosphate Gene in Ulcerative Colitis.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease that can lead to malignancies over time. Sphingosine-1-phosphate (S1P) receptor signaling affects lymphocyte trafficking and vascular integrity, influencing intestinal inflammation. This study aimed to identify S1P-related key genes in UC. METHODS: Differentially expressed genes (DEGs) between the UC and control groups were analyzed in the GSE87473 (training) dataset. Genes overlapping between the DEGs and S1P-related genes were considered candidate genes. These genes were incorporated into machine learning algorithms and subjected to expression analysis to identify key genes. Gene functions were determined through a gene–gene interaction network, enrichment analysis, and immune cell infiltration analysis. In addition, transcription factor–mRNA and mRNA–miRNA–lncRNA networks were constructed. Finally, reverse transcription–quantitative polymerase chain reaction (RT-qPCR) was performed to evaluate the expression of key candidate genes in UC and control tissues. RESULTS: This study identified two key genes (SPHK2 and SPNS2) associated with UC. Notably, SPHK2 expression was lower and SPNS2 expression was higher in the UC group in both training and validation datasets and in clinical UC tissues (RT-qPCR). The area under the curve values of SPHK2 and SPNS2 exceeded 0.7 in both datasets, indicating that the genes had good diagnostic efficacy for UC. Consistently, the nomogram showed that the two genes had promising diagnostic value in UC. SPHK2 and SPNS2 were found to be localized to the plasma membrane. The correlations of the two genes with different immune cells showed significantly opposite trends. In particular, SPHK2 had the strongest positive correlation with M2 macrophages (r = 0.6) and the strongest negative correlation with neutrophils. Moreover, mRNA–miRNA–lncRNA and transcription factor– mRNA networks of the key genes were constructed. CONCLUSION: This study suggests that SPHK2 and SPNS2 are key genes associated with UC, highlighting their potential as effective diagnostic biomarkers.

Humans↗

PubMed2026

Glucose-6-phosphate dehydrogenase variants modify 3D genomic organization to suppress maladaptive gene expression and vascular disease.

The 3D genome architecture is a higher-order organization of chromosomes within the nucleus that is critical to the control of epigenomic modifications. However, our knowledge regarding the role of 3D genomic organization in the regulation of vascular gene expression and function is lacking. In the present study, CRISPR-engineered rats modelled after two common polymorphisms (S188F and N126D) in human glucose-6-phosphate dehydrogenase (G6PD) revealed modifications to the 3D genome in aortas from rats expressing a deficient G6PD variant (S188F), but not a non-deficient one (N126D), is associated with: 1] up-regulated expression of TET enzymes that augmented expression of genes encoding antiproliferative proteins, 2] suppressed expression of genes encoding inflammatory/thrombotic/fibrotic proteins, and 3] reduced angiotensin II-induced aortic stiffness and hypertension. G6PD interacted with MATRIN-3, a nuclear matrix/scaffold protein, and a deficient G6PD variant increased the relative abundance of MATR3 and CCCTC-binding factors, potentially modifying 3D-genome structure. Additionally, G6PD deficiency-induced enrichment of H3K27ac likely influences the establishment and maintenance of the 3D genome. Therefore, we propose that the nexus between metabolism and the 3D genome regulates arterial gene expression and vascular disease.

Animals↗