SEARCH · Search PubMed

Results for “transcriptomic profiling”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5Linked to original sources

PubMed2026

Attribution of PM2.5-Induced Transcriptomic Perturbation to Toxic Components.

Ambient fine particulate matter (PM2.5) is a chemically complex mixture whose health impacts are not fully captured by particle mass. Here, we developed an interpretable chemotranscriptomic framework to attribute PM2.5-induced molecular perturbations to toxicity-relevant components. PM2.5 collected from urban roadside and coastal environments was separated into whole, extractable, and unextractable fractions, characterized by LC/GC × GC-HRMS-based nontarget analysis and inductively coupled plasma mass spectrometry (ICP-MS), and evaluated using cytotoxicity testing and transcriptomic profiling in human bronchial epithelial cells. Urban PM2.5 exhibited greater cytotoxic potency per unit mass than coastal PM2.5, with extractable fractions accounting for most cytotoxic and pathway-level responses. Transcriptomics revealed distinct site-specific modes of action: urban PM2.5 preferentially induced oxidative stress, xenobiotic metabolism, and cell cycle suppression, consistent with acute, nonapoptotic injury, whereas coastal PM2.5 elicited weaker cytotoxicity but stronger interferon-mediated immune and apoptosis-related signaling. Integrating chemical abundance with pathway activity using random forest regression, SHAP interpretation, and mechanistic corroboration reduced 5,033 detected features to 444 pathway-linked candidate drivers. Fewer than 5% of features explained ∼95% of cumulative model contribution. Standard-confirmed contributors included plasticizer-related compounds, aromatic and heteroaromatic combustion products, and copper for urban PM2.5 and secondary/aged organics and nickel for coastal PM2.5. These findings support mechanism-informed prioritization of hazardous PM2.5 components beyond mass-based assessment.

Particulate Matter↗

PubMed2026

Distinct periarticular muscle transcriptomes: inflammation in rheumatoid arthritis versus metabolic dysregulation in osteoarthritis.

OBJECTIVES: Periarticular skeletal muscle abnormalities are recognised in rheumatoid arthritis (RA) and osteoarthritis (OA), but their divergent molecular pathologies are poorly defined. This study aimed to elucidate and directly compare the transcriptomic profiles of periarticular muscle in patients with RA and OA. METHODS: We performed bulk RNA sequencing of periarticular skeletal muscle samples collected during total joint arthroplasty from RA (n=6) and OA (n=4) patients. Differential gene expression analysis, weighted gene co-expression network analysis (WGCNA), pathway enrichment, and gene set variation analyses were conducted to identify disease-specific molecular features and their clinical associations. RESULTS: The two conditions showed fundamentally distinct profiles. RA muscle exhibited a pronounced inflammatory signature, characterised by upregulation of cytokine-responsive genes including FOS, EGR1, and CXCL2, and enrichment of tumour necrosis factor-α and interleukin-6 (IL-6)/JAK-STAT3 signalling. In contrast, OA muscle was characterised by metabolic dysregulation, with upregulation of genes linked to adipogenesis (PCK1, SFRP4) and significant enrichment of epithelial-to-mesenchymal transition (EMT) signalling. These divergent profiles were further supported by WGCNA, which identified distinct modules reflecting heightened innate immune and complement activation in RA, and disrupted metabolic processes in OA. Notably, in RA, the IL-2-STAT5 signalling pathway was unique among those tested in showing a strong positive correlation with DAS28-ESR (r=0.94, p=0.019). CONCLUSIONS: This study reveals distinct molecular pathologies in the periarticular muscle of RA and OA. RA muscle shows an intense inflammatory profile potentially linked to cachexia, whereas OA muscle displays features of metabolic disease and pro-fibrotic remodelling.

Humans↗

PubMed2026

Uncovering molecular regulatory networks of low-temperature stress response in Trachinotus ovatus via integrated transcriptome and metabolome analyses.

Golden pompano (Trachinotus ovatus) is one of the most economically important marine fish species in China. It is susceptible to low-temperature stress, which significantly challenges its production and supply. Nevertheless, study on the regulatory mechanisms underlying low-temperature stress responses in golden pompano remains limited. Here, we firstly performed a time-series transcriptome analysis to reconstruct dynamic response patterns under low-temperature stress in golden pompano. Transcriptome profiling identified common differentially expressed genes (DEGs), including fos, hlf, and hmgb1, as well as condition-specific DEGs across distinct low-temperature stress groups. Based on cluster analysis, all DEGs were classified into five distinct expression patterns, reflecting diversified regulation of expression in golden pompano during low-temperature stress. Furthermore, condition-specific regulatory modules were explored via weighted gene co-expression network analysis (WGCNA), highlighting that the two module hub genes, serbf2 and lipc, might respond to low-temperature stress by regulating the lipid catabolic process. Subsequently, untargeted metabolomic analysis revealed that glycerophospholipid metabolism was a significantly enriched common pathway, highlighting its crucial role in mediating the response to low-temperature stress. Finally, by integrating transcriptomic and metabolomic analyses, a gene-metabolite interaction network associated with glycerophospholipid metabolism under low-temperature stress was established. These findings underscore the significance of multiple candidate genes and glycerophospholipid metabolism in golden pompano's response to low-temperature stress, thereby laying a solid molecular foundation for the development of low-temperature-tolerant fish strains.

Animals↗

PubMed2026

SSB deficiency-induced R-loop accumulation triggers podocyte inflammation in DKD.

INTRODUCTION: Diabetic kidney disease (DKD) is fundamentally a podocytopathy in which sterile inflammation plays a central pathogenic role, yet the upstream triggers that initiate inflammatory cascades in podocytes remain elusive. R-loops are critical regulators of genomic stability, and their pathological accumulation triggers DNA damage and innate immune activation. Whether R-loop dysregulation contributes to podocyte-driven inflammation in DKD is unknown. METHODS: We integrated single-cell transcriptomic profiling, dual machine learning algorithms, and functional experiments to dissect the R-loop regulatory network in the diabetic kidney. RESULTS: Integrated analysis of human diabetic kidney single-cell RNA-seq data revealed a globally compromised R-loop regulatory network selectively within podocytes. Intersection of podocyte-specific transcriptomic shifts with validated R-loop regulators identified 93 candidate genes, from which dual machine learning algorithms pinpointed SSB (Sjögren syndrome antigen B) as the principal podocyte-selective R-loop resolver and a superior diagnostic biomarker (AUC = 0.983). SSB expression was selectively downregulated in diabetic podocytes and showed the strongest positive correlation with the R-loop resolution module. Mechanistically, SSB loss impaired RNA splicing and stability pathways, leading to aberrant R-loop accumulation that activated the cGAS-dependent inflammatory signaling in podocytes. In two murine DKD models and high glucose-challenged podocytes, SSB was markedly reduced. Remarkably, SSB knockdown in podocytes alone sufficed to trigger R-loop accumulation and pro-inflammatory cytokine expression, whereas both RNase H1-mediated R-loop removal and cGAS co-depletion blunted this response. DISCUSSION: These findings suggest that an SSB-governed R-loop -cGAS -inflammatory signaling axis may link genomic instability to podocyte inflammation and contribute to DKD progression, nominating R-loop homeostasis as a previously unrecognized potential therapeutic target.

Podocytes↗

PubMed2026

Genomic and transcriptomic characterization of genes expressed at 20 MPa by the marine actinobacterium Kocuria flava.

A marine hydrocarbonoclastic actinobacterium Kocuria flava IOS11 was isolated from 3500 m deep-sea water of the Indian Ocean. The isolate efficiently degraded phenanthrene (250 mg/L) achieving 82 and 98% of degradation at 0.1 MPa and 20 MPa, respectively within a period of 5 days. Whole genome, transcriptomee and metabolomic analysis elucidated its phenanthrene biodegradation efficiency under in situ deep-sea conditions. The genome sequence comprises 3.47 Mb distributed across 88 scaffolds with a high GC content of 74.30%. The genome analysis encoded 3126 genes including 3052 protein coding sequences with functional annotation identifying a broad array of genes associated with PAHs degradation, environmental stress adaptation, biosurfactant and siderophore synthesis. Transcriptome profiling under 0.1 and 20 MPa conditions with phenanthrene as a sole carbon source revealed enhanced expression of hydrocarbon degrading genes, transporters, biosurfactant associated enzymes and stress responsive genes including integrases, DNA repair protein Rad, alanine ligase, heat and cold shock proteins under high pressure conditions underscoring the deep-sea adaptation capabilities of the strain. The degradation pathway of phenanthrene was proposed through integrated genome, transcriptome and metabolomic analysis. These studies provided K. flava IOS11 as a metabolically versatile and pressure adapted bacterium with promising potential for bioremediation application in extreme marine environment.

Transcriptome↗

PubMed2026

Integrated multi-omic profiling enables recurrence risk stratification beyond pathological stage in resected EGFR-mutant lung adenocarcinoma.

BACKGROUND: Early-stage EGFR-mutant lung adenocarcinoma (LUAD) demonstrates heterogeneous outcomes after curative surgery, yet adjuvant treatment decisions are guided by pathological stage alone. Following the ADAURA trial, adjuvant osimertinib is the standard of care for resected stage IB-IIIA EGFR-mutant LUAD; however, real-world data demonstrate that up to 40% of patients remain disease-free at five years without adjuvant osimertinib, underscoring the need for improved risk stratification. PATIENTS AND METHODS: We performed integrated clinical, genomic and transcriptomic profiling of 400 patients with resected stage IA-IIIA EGFR-mutant LUAD. EGFR-mutant recurrence risk models integrating clinical, genomic and transcriptomic data were developed and validated across one internal and three external cohorts. RESULTS: Genomic instability, including TP53 co-mutations, copy number alterations and APOBEC-associated mutational signatures, increased with pathological stage. RBM10 co-mutations were enriched in tumours with L858R mutations and correlated with upregulation of WNT signalling and epithelial-mesenchymal transition. Transcriptomic features outperformed clinical or genomic variables alone in predicting recurrence risk, and a multi-omic model demonstrated superior and reproducible performance, achieving a median concordance index of 75.4% across four independent validation cohorts. The multi-omic model stratified recurrence risk within individual pathological stages, including stage I disease, and identified patients most likely to benefit from adjuvant EGFR TKI. CONCLUSIONS: These findings define the molecular heterogeneity of early-stage EGFR-mutant LUAD and support multi-omic risk stratification to inform adjuvant EGFR TKI decisions beyond pathological stage. Prospective validation in larger cohorts will be required to confirm these findings.

Journal Article↗

PubMed2026

TNIK Overexpression Is Sufficient for Chemoradiation Resistance in Limited-Stage Small Cell Lung Cancer.

Small cell lung cancer (SCLC) is characterized by early metastasis, intrinsic chemoradiation resistance, and tumor recurrence. Besides the lack of potentially targetable oncogenic drivers, therapeutic advancements are also hindered by the scarcity of surgically resected tissue specimens ideal for profiling studies. We used patient-derived xenografts (PDX) to model SCLC chemoradiation resistance and identified chemoradiation resistance candidate genes using RNA sequencing. Additionally, we used human SCLC cell lines to confirm our in vivo results and delineate the underlying mechanism. Transcriptome profiling showed that the Traf2- and Nck-interacting kinase (TNIK) gene was consistently upregulated in an array of SCLC PDXs exposed to chemoradiation compared with monotherapy, which is consistent with previous observations of TNIK amplification in human samples. Genetic depletion (P < 0.01) or pharmacologic inhibition (P < 0.0001) of TNIK reduced in vitro clonogenic survival of TNIKhigh SCLC cells and promoted sensitivity to chemoradiation. In vivo, pharmacologic inhibition of TNIK enhanced chemoradiation sensitivity (P < 0.0001) of the H446 cell line-derived xenograft (CDX) in NOD-SCID mice. Furthermore, pharmacologic inhibition of TNIK in vivo demonstrated sensitivity (P < 0.0001) to chemoradiotherapy (CRT) in LX33 PDX. These results indicate that TNIK plays a role in conferring resistance to chemoradiation in SCLC cell lines and in vivo in SCLC CDX and PDX models. Delineating the mechanism behind radiosensitization suggested that TNIK inhibition may impair the DNA damage response in irradiated cells. Collectively, these findings suggest that TNIK may be a promising therapeutic target in limited-stage SCLC and support further investigation of TNIK inhibition in combination with standard CRT.

Humans↗

PubMed2016

Loss of neurogenesis in Hydra leads to compensatory regulation of neurogenic and neurotransmission genes in epithelial cells.

Hydra continuously differentiates a sophisticated nervous system made of mechanosensory cells (nematocytes) and sensory-motor and ganglionic neurons from interstitial stem cells. However, this dynamic adult neurogenesis is dispensable for morphogenesis. Indeed animals depleted of their interstitial stem cells and interstitial progenitors lose their active behaviours but maintain their developmental fitness, and regenerate and bud when force-fed. To characterize the impact of the loss of neurogenesis in Hydra, we first performed transcriptomic profiling at five positions along the body axis. We found neurogenic genes predominantly expressed along the central body column, which contains stem cells and progenitors, and neurotransmission genes predominantly expressed at the extremities, where the nervous system is dense. Next, we performed transcriptomics on animals depleted of their interstitial cells by hydroxyurea, colchicine or heat-shock treatment. By crossing these results with cell-type-specific transcriptomics, we identified epithelial genes up-regulated upon loss of neurogenesis: transcription factors (Dlx, Dlx1, DMBX1/Manacle, Ets1, Gli3, KLF11, LMX1A, ZNF436, Shox1), epitheliopeptides (Arminins, PW peptide), neurosignalling components (CAMK1D, DDCl2, Inx1), ligand-ion channel receptors (CHRNA1, NaC7), G-Protein Coupled Receptors and FMRFRL. Hence epitheliomuscular cells seemingly enhance their sensing ability when neurogenesis is compromised. This unsuspected plasticity might reflect the extended multifunctionality of epithelial-like cells in early eumetazoan evolution.

Animals↗

PubMed2026

Phenotypic, physiological and transcriptomic analysis of graded salt stress responses in Pyrus betulifolia Bunge and functional characterization of the hub gene PbSTY46.

Pyrus betulifolia Bunge is a salt‑tolerant rootstock for pear, but its salt‑tolerance mechanisms remain largely unknown. In this study, P. betulifolia seedlings were subjected to graded NaCl stress at concentrations of 0 (CK), 50 (T1), 100 (T2), and 200 (T3) mM. We integrated phenotypic observation, physiological assessment, transcriptomic profiling, and functional gene validation to systematically elucidate its salt tolerance mechanisms. Salt stress inhibited seedling growth and root traits in a concentration-dependent manner, and T3 caused the most severe damage. Osmotic solutes responded differentially: soluble sugars peaked under T2, while proline peaked under T3. Antioxidant enzymes showed tissue-specific biphasic responses and declined after prolonged T3 stress. Meanwhile, chlorophyll and photosynthesis decreased, whereas anthocyanin increased, indicating a metabolic shift from photosynthesis to photoprotection. Transcriptome analysis revealed distinct responses depending on stress intensity: mild stress induced membrane lipid remodeling, moderate stress activated circadian rhythm and hormone signaling, and severe stress enhanced phenylpropanoid biosynthesis and thiamine metabolism. Gene Set Enrichment Analysis (GSEA) further highlighted progressive enrichment of phenylpropanoid biosynthesis, heme binding, and oxidoreductase activity. Weighted Gene Co‑expression Network Analysis (WGCNA) identified a blue module significantly positively correlated with root traits, from which the hub gene PbSTY46 was identified. Functional validation via overexpression, loss‑of‑function mutants, and pharmacological interventions (MeJA/DIECA) confirmed that PbSTY46 acts through JA signaling to enhance antioxidant enzyme activities and thereby confer salt tolerance. Collectively, P. betulifolia adopts a "survival‑first" strategy that coordinates growth arrest, osmotic homeostasis, and ROS scavenging. These findings establish PbSTY46 as a key regulator that links JA signaling to antioxidant defense. Thus, PbSTY46 represents a promising candidate for marker‑assisted breeding of salt‑tolerant pear cultivars.

Salt Stress↗

PubMed2025

Proteomic snapshot of pattern triggered immunity in the Arabidopsis leaf apoplast.

The apoplast is a critical interface in plant-pathogen interactions, particularly in the context of pattern-triggered immunity (PTI), which is initiated by recognition of microbe-associated molecular patterns. Our study characterizes the proteomic profile of the Arabidopsis apoplast during PTI induced by flg22, a 22-amino-acid bacterial flagellin epitope, to elucidate the output of PTI. Apoplastic washing fluid was extracted with minimal cytoplasmic contamination for liquid chromatography-tandem mass spectrometry analysis. By comparing our data to publicly available transcriptome profiles of flg22 treatment from 1 to 18 h, we observed that several highly abundant proteins exhibit relatively unchanged gene expression across all time points. We also observed topological bias in peptide recovery of 19 enriched receptor-like kinases with peptides predominantly recovered from their ectodomains. Notably, tetraspanin 8, an exosome marker, was enriched in PTI samples. We additionally confirmed increased concentrations of exosomes during PTI. This study enhances our understanding of the proteomic changes in the apoplast during plant immune responses and lays the groundwork for future investigations into the molecular mechanisms of plant defense under recognition of pathogen molecular patterns.

Arabidopsis↗

PubMed2026

A weakly supervised deep learning-based recurrence prediction and risk stratification of lung adenocarcinoma from pathology whole-slide images.

BACKGROUND: Accurate prediction of postoperative recurrence in lung adenocarcinoma (LUAD) is essential for guiding clinical decision-making and improving patient outcomes. Although various predictive models have been developed, most rely on complex genomic analyses and high-dimensional clinical data. The complexity of these approaches substantially limits their feasibility for routine clinical use. To address this clinical challenge, this study aims to predict postoperative recurrence using routinely available hematoxylin and eosin (H&E)-stained images and characterize the associated biological features. METHODS: A total of 329 patients who underwent curative resection at the First Affiliated Hospital of Wenzhou Medical University (FHWMU) were retrospectively enrolled and randomly assigned to training and internal validation cohorts in a 7:3 ratio. An independent external validation cohort comprising 70 patients from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) was included. Three patch-level feature extractors (Inception_V3, ResNet18, and DenseNet121) were evaluated within a weakly supervised multiple-instance learning (MIL) framework incorporating automated region-of-interest (ROI) detection on segmented whole-slide images (WSIs). Model performance was assessed using the area under the receiver operating characteristic curve (AUC), Kaplan-Meier (KM) survival analysis, and multivariable Cox proportional hazards regression. Transcriptomic profiling and gene set enrichment analysis (GSEA) were conducted to investigate biological differences between risk groups. RESULTS: The model achieved AUCs of 0.923 in the training cohort, 0.891 in the internal validation cohort, and 0.847 in the external validation cohort. The model effectively stratified patients into high- and low-risk groups with significantly different recurrence-free survival (RFS) across all cohorts (all P < 0.001) and retained prognostic value within AJCC stages I-III. Transcriptomic analyses revealed consistent enrichment of cell cycle-related pathways and neutrophil extracellular trap (NET) formation in high-risk patients across both institutional and CPTAC cohorts, aligning with distinct biological profiles of the model-derived risk stratification. CONCLUSIONS: This weakly supervised deep learning framework enables accurate and externally validated prediction of postoperative recurrence in LUAD using routinely available histopathological images, and integration of histopathological features with molecular analyses enhances biological interpretability. This work provides a clinically accessible and cost-effective tool for postoperative risk assessment in LUAD patients.

Humans↗

PubMed2026

Amino-acids-mTORC1-driven DDA1 phosphorylation promotes DNA repair and glioblastoma progression.

BACKGROUND: DDA1 is a protein involved in protein degradation, cell cycle regulation, and DNA damage repair. Although its expression varies across tumor types, the precise role of DDA1 in gliomagenesis remains unclear. METHODS: We investigated the function of DDA1 in multiple glioblastoma cell models using biochemical assays, phosphorylation analysis, subcellular localization studies, and integrated genomic and transcriptomic profiling to determine its signaling interactions and downstream effects. RESULTS: We identified a physical association between cytoplasmic DDA1 and Raptor, a core component of lysosome-associated mTORC1. Amino acid stimulation triggered phosphorylation of DDA1 at serine 33 promoting its nuclear translocation and involvement in DNA damage repair. Integrated transcriptomic analyses revealed that the mTORC1-DDA1S33-DNA repair axis regulates the expression of a subset of metabolic genes, including ENO2, CA12, and NMRK1. Functional assays further suggested that these genes contribute to the survival capacity of glioblastoma cells, particularly under DDA1-deficient conditions. Consistently, DDA1 deficiency markedly impaired glioblastoma growth and induced compensatory upregulation of metabolic activity. CONCLUSION: Our findings identify DDA1 as a previously unrecognized phosphorylation target downstream of mTORC1 and a critical mediator of the mTORC1 driven DNA damage response. Through its involvement in DNA repair and metabolic gene regulation, DDA1 appears to support glioblastoma progression, providing mechanistic insight into mTORC1 related gliomagenesis and suggesting potential therapeutic relevance.

Glioblastoma↗

PubMed2025

Rare variants in MIR184 are a novel genetic cause of Fuchs endothelial corneal dystrophy.

PURPOSE: To identify novel genetic causes of Fuchs endothelial corneal dystrophy (FECD) within a genetically unsolved patient cohort lacking repeat expansions in the TCF4 gene (Exp-). METHODS: A rare variant analysis framework (CoCoRV) was applied to exome data, in combination with in silico modeling, luciferase reporter, and RNA-seq analysis to characterize transcriptome-wide consequences of identified variants. RESULTS: A gene burden analysis identified MIR184, a microRNA encoding gene, to be enriched for rare pathogenic variants within the studied Exp- FECD cohort. In total, 2 noncoding rare variants were identified in 4 unrelated FECD probands: NR_029705.1:n.58G>A and n.73G>T. Both variants altered highly conserved mature sequence residues, were predicted to induce hairpin structural changes, and were experimentally determined to disrupt microRNA-mRNA interactions. RNA-seq of transfected human corneal endothelial cells revealed that the mutants elicited distinct transcriptomic profiles. Enriched KEGG pathways included PI3K-Akt signaling, focal adhesion, and immune response, revealing shared pathogenic mechanisms between MIR184-associated FECD and the more common TCF4 repeat expansion-mediated form of disease. CONCLUSION: MIR184 variants are a novel rare genetic cause of FECD, and common pathways of transcriptomic dysregulation are shared across genetically distinct subtypes of the disease. These pathways may serve as future gene agnostic targets for therapeutic interventions.

Humans↗

PubMed2026

EGFR-Mutant Non-Small Cell Lung Cancer With Small Cell Transformation: Clinicopathological Features, Treatment Landscape, and Biomarker Profiles.

INTRODUCTION: Transformed small-cell lung cancer (tSCLC) is a clinically important resistance mechanism to EGFR tyrosine kinase inhibitors in EGFR-mutant non-small cell lung cancer. This study characterizes clinical features, treatment outcomes, and biomarker profiles in patients with tSCLC. METHODS: Data from 45 patients with EGFR-mutant NSCLC who developed tSCLC between 2014 and 2023 were analyzed. Demographic characteristics, treatment histories, and delta-like ligand 3 (DLL3) and B7-H3 expression were collected. Objective response rate, progression-free survival (PFS), and posttransformation survival (PTS) were assessed. Spatial transcriptomic profiling was performed in selected cases. RESULTS: Most patients were women (60%) and never-smokers (75.6%). Exon 19 deletion was the predominant EGFR mutation (57.8%). Median PFS and PTS were 3.3 and 9.2 months, respectively. Etoposide plus platinum (EP) was the predominant first-line regimen (69.8%), with 23.2% of the patients receiving EP plus immune checkpoint or tyrosine kinase inhibitors. EP-based combination regimens yielded a numerically higher objective response rate and a significantly longer PFS than EP alone (7.5 versus 2.8 months, p = 0.002). PTS was longer with EP-based regimens than with other regimens (10.4 versus 6.4 months, p = 0.035). DLL3 and B7-H3 were expressed in 87.5% and 66.7% of tumors, respectively, without prognostic significance. Multivariable analysis identified brain metastasis and liver progression at transformation as adverse prognostic factors. Spatial transcriptomic analysis revealed neuroendocrine lineage reprogramming, stromal depletion, and immune exclusion. CONCLUSIONS: tSCLC remains an aggressive resistance phenotype with poor outcomes. EP-based combination strategies may provide clinical benefit, whereas frequent DLL3 expression supports further evaluation of targeted therapies.

Delta-like ligand 3↗

PubMed2026

Downregulation of Trpv4 and Klf2 in brain microvessels is associated with the progression of neurovascular dysfunction and cognitive impairment in a model of heart failure with preserved ejection fraction.

Vascular cognitive impairment (VCI) shares major risk factors with heart failure with preserved ejection fraction (HFpEF), including obesity, diabetes and hypertension. Yet VCI research often relies on single-stimulus models, whereas patients experience combined risk factors. We therefore assessed cerebrovascular and cognitive phenotypes in an HFpEF model and investigated underlying mechanisms. Male Lean and Obese ZSF1 rats underwent longitudinal assessments of blood pressure, glucose, cardiac function and behavioural performance. Cerebral blood flow and neurovascular coupling were assessed by laser speckle contrast imaging. White matter integrity, blood-brain barrier (BBB) permeability and vascular density were analyzed by (immuno)histochemistry. Cortical microvessels were isolated for transcriptomic profiling, and selected targets were validated using multiplex in-situ hybridization. Obese rats exhibited neurovascular uncoupling and impaired short- and long-term memory and spatial learning, accompanied by brain atrophy and reduced myelin. BBB permeability increased at 22-23 weeks and vascular density at 34-35 weeks in Obese versus Lean rats. Transcriptomic analysis of brain microvessels revealed altered processes related to angiogenesis, vasoreactivity, immune mechanisms and vascular remodelling, with consistent downregulation of Trpv4 and Klf2. Obese ZSF1 rats develop progressive neurovascular dysfunction associated with HFpEF onset and reduced Trpv4 and Klf2 expression in cerebral microvessels, two key vasoprotective genes.

Diastolic dysfunction↗

PubMed2025

Comprehensive analysis of DNA methylome and transcriptome reveals the epigenetic regulation of nitric oxide treatment in delaying apricot fruit senescence.

Apricot produces climacteric fruit, which are perishable after harvest. To elucidate the regulatory role of NO treatment through DNA methylation in post-harvest senescence, apricot fruits were treated with 0.2 mmol/L sodium nitroprusside (SNP) solution for 10 min, with distilled water treatment serving as the control. Treated fruits were then stored at 25°C and 80% relative humidity. Changes in appearance quality, physiological parameters, metabolome profiles, transcriptome dynamics, and DNA methylation patterns were analyzed before and after storage. Results showed that NO treatment delayed apricot softening, increased flavonoid metabolite accumulation, and reduced lipid and abscisic acid accumulation, with these effects correlated to the expression of specific genes and transcription factors. This work reveals the epigenetic regulatory mechanism underlying NO treatment delaying ripening and senescence. Further analysis revealed that the transcription levels of ACO, PAL, UFGT-like, NCED1, PP2C, MYB21, CCoAOMT-like, CYP707A, and ZNF7-like were all correlated with DNA methylation. This indicates that SNP treatment can lead to large changes in DNA methylation levels in apricot fruits, and that the differences in gene transcription levels are associated with the occurrence of hypomethylation and hypermethylation. Collectively, these findings establish an epigenetic framework for post-harvest regulation of apricot fruit, revealing DNA methylation-mediated freshness preservation mechanisms.

DNA Methylation↗

PubMed2026

Targeting USP22 reprograms the tumor microenvironment and sensitizes KRAS/p53-driven lung cancer to anti-PD-1 immunotherapy.

RATIONALE: Ubiquitin-specific peptidase 22 (USP22), a deubiquitinase and component of the "Death-from-Cancer" 11-gene signature, is overexpressed in multiple malignancies and linked to recurrence, therapy resistance, and poor prognosis. Its role in KRAS/p53-driven lung cancer and the response to immune checkpoint inhibitors (ICIs) remains poorly defined. Here, we investigated USP22 as a potential therapeutic target in KRAS/p53-driven lung cancer. METHODS: A conditional Usp22 knockout (Usp22-KO) was generated in the KRASG12D; p53-/- (KP) mouse model. Cancer progression was monitored by micro-computed tomography (micro-CT). Multiplex immunofluorescence (mIF), RNA sequencing, and spatial transcriptomics profiled cancer and tumor microenvironment (TME) changes. Responses to anti-PD-1/PD-L1 therapies were compared between KP and Usp22-KO KP (KPU-) lung cancers. RESULTS: USP22 was highly expressed in early-stage KRAS/p53-driven mouse lung cancers and strongly correlated with proliferation marker Ki67. Usp22 deletion suppressed cancer growth, prolonged survival, and promoted cancer differentiation. Spatial transcriptomics and mIF revealed reduced CD206+ M2 macrophages, myeloid-derived suppressor cells (MDSCs), TGF-β1, and angiogenesis, along with increased functional CD8+ T cells. Mechanistically, USP22 regulated gene expression and protein stability, reducing c-Myc, PD-L1, TGF-β1, and SPARC upon Usp22 loss. Compared with KP cancer, KPU- and SPARC-knockdown KP cancers showed reduced macrophage chemotaxis and impaired basal- and TGF-β1-induced M2 polarization of RAW264.7 cells, suggesting that TGF-β1 and SPARC downregulation partially contributes to decreased M2 macrophage infiltration in KPU- cancers. Notably, Usp22 loss enhanced the efficacy of anti-PD-L1 and anti-PD-1 therapies in orthotopic and subcutaneous KP lung cancer models, respectively. USP22 and SPARC expression were also strongly correlated in human lung cancers. CONCLUSIONS: USP22 promotes progression and immune evasion in KRAS/p53-driven lung cancer. Targeting USP22 reprograms the TME, suppresses oncogenic signaling, and sensitizes tumors to ICI, establishing USP22 as a promising therapeutic target.

Animals↗

PubMed2026

Genome-wide identification of WOX transcription factors and functional characterization of WOX4 and WOX13 involved in cold stress response in Malus baccata.

INTRODUCTION: Cold stress is a major abiotic threat to apple production. Malus baccata has exceptional cold hardiness and is widely used as a superior cold-resistant rootstock. The WUSCHEL-related homeobox (WOX) transcription factor family regulates plant growth, development and stress adaptation, whereas the functions of WOX genes in cold tolerance of M. baccata remain elusive. METHODS: In the present work, 19 MbWOX family members were identified and characterized at the genome-wide level. Evolutionary analysis, cis-element prediction, transcriptome profiling and real-time quantitative PCR (RT-qPCR) were performed to screen core cold-responsive genes. Overexpression vectors were constructed and transformed into Arabidopsis seedlings for functional verification. RESULTS: Evolutionary analysis revealed that segmental duplication drove the expansion of the MbWOX family, and these genes contained a variety of stress-responsive cis-elements. Combined transcriptome and RT-qPCR analyses confirmed that MbWOX4 and MbWOX13 were core cold-responsive genes with distinct expression patterns. The two genes participated in cold signal transduction by interacting with different transcription factor networks. Functional tests revealed that MbWOX4 and MbWOX13 isoforms differentially modulated seedling cold tolerance under low-temperature stress.

Malus baccata↗