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PubMed2026

Coordinated inflammatory macrophage and vascular smooth muscle cell remodeling signatures in human atherosclerosis: An integrative single-cell and bulk transcriptomic analysis.

Atherosclerotic plaque progression is shaped by coordinated inflammatory and remodeling programs involving immune cells and vascular wall cells. Inflammatory macrophage activation and vascular smooth muscle cell (VSMC) phenotypic remodeling are central features of human atherosclerosis, but their transcriptomic relationships during plaque progression remain incompletely characterized. This study integrated single-cell and bulk transcriptomic datasets to examine highly inflammatory macrophage states, VSMC remodeling-related transcriptional programs, and candidate ligand-receptor expression patterns in human atherosclerotic plaques. Human atherosclerotic plaque single-cell RNA sequencing data from GSE260657 and bulk transcriptomic data from GSE28829 were analyzed. After quality control, 7628 cells were retained for single-cell analysis. Major cell types were annotated using canonical markers, followed by reclustering of macrophages and VSMC-related cells. Functional module scoring, differential expression analysis, Gene Ontology biological process enrichment, and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to characterize macrophage transcriptional states. Slingshot was applied to infer VSMC pseudotime ordering. CellChat and NicheNet were used to prioritize candidate ligand-receptor expression patterns and ligand-associated VSMC target gene programs. External bulk transcriptomic analysis was performed to examine whether single-cell-derived inflammatory and remodeling signatures were represented at the tissue-transcriptome level during plaque progression. Macrophage reclustering identified a highly inflammatory macrophage state characterized by prominent inflammatory activation, cytokine-response, and stress-response features. Genes upregulated in this population were enriched in pathways related to tumor necrosis factor (TNF) response, nuclear factor kappa B signaling, leukocyte activation, cytokine signaling, lipid and atherosclerosis, toll-like receptor signaling, and inflammasome-associated inflammation. VSMC reclustering revealed contractile VSMCs, PTHLH+ synthetic VSMCs, KRT7+ VSMC-like cells, interferon-responsive VSMCs, pericyte-like mural cells, and osteogenic/modulated VSMCs. Pseudotime analysis showed a broad contractile-to-osteogenic/modulated transcriptional continuum accompanied by increased expression of remodeling-associated genes and selected inflammatory or remodeling-associated receptor genes. CellChat and NicheNet analyses prioritized candidate ligand-receptor and ligand-associated target gene expression patterns involving SPP1-CD44, TNF-TNFRSF1A, IL1B-IL1R1/IL1RAP, MIF-ACKR3, PDGFB-PDGFRB, and FN1-SDC1/ITGB1. In GSE28829, inflammatory macrophage-, osteogenic/modulated VSMC-, candidate ligand-receptor expression-, SPP1-CD44 candidate axis-, and NicheNet-prioritized target program-related signatures were more prominent in advanced plaques and were positively correlated with each other. This integrative transcriptomic analysis identified a highly inflammatory macrophage state and a VSMC remodeling continuum in human atherosclerotic plaques. Candidate ligand-receptor and ligand-associated target gene expression patterns linked inflammatory macrophage activation with osteogenic/modulated VSMC remodeling at the computational level. External bulk data further showed coordinated enrichment of inflammatory and remodeling signatures in advanced plaques. These findings provide a descriptive and hypothesis-generating transcriptomic framework for understanding inflammatory macrophage activation and VSMC remodeling in human atherosclerosis.

atherosclerosis↗
PubMed2026

Early Fibrotic Remodeling Remains Responsive to Autologous Fat Grafting: Histological Findings in a Rat Model.

BACKGROUND/AIM: Fibrosis-associated soft tissue remodeling involves progressive alterations in extracellular matrix composition, vascular architecture and tissue biomechanics. Early fibrotic lesions may remain biologically responsive before irreversible sclerosis develops. This study evaluated the histological evolution of bleomycin-induced soft tissue remodeling and the effects of autologous fat grafting in a rat model. MATERIALS AND METHODS: Twenty female Wistar rats received subcutaneous bleomycin (1 mg/kg/day for three consecutive days) to induce localized soft tissue remodeling. Autologous fat grafting was performed 17 days later. Clinical assessment was conducted at baseline, Day 17 and Day 31 using a standardized semi-quantitative score evaluating erythema, edema, skin elasticity, cutaneous mobility and ulceration or necrosis. Histological analysis was performed at predefined timepoints. RESULTS: Bleomycin induced reproducible early fibrotic remodeling characterized by collagen deposition, stromal hypercellularity, vascular remodeling and architectural distortion. The mean composite clinical score increased from 0 at baseline to 9.10±1.75 on Day 17 and decreased to 7.75±1.35 after fat grafting on Day 31 (p=0.00024). Histological examination demonstrated persistent fibrotic septa, fibroblast proliferation, vascular reorganization and partial integration of grafted adipose tissue, indicating ongoing tissue remodeling. CONCLUSION: Bleomycin-induced remodeling produced reproducible early fibrotic changes in dermal and subcutaneous tissues. Autologous fat grafting was associated with significant clinical improvement and histological evidence of continued tissue reorganization. This model supports investigation of regenerative therapies targeting early fibrosis-associated soft tissue remodeling.

Animals↗
PubMed2024

S100A9 induces tissue remodeling of human nasal epithelium in chronic rhinosinusitis with nasal polyp.

BACKGROUND: Chronic inflammation triggers tissue remodeling in human nasal epithelial (HNE) cells. S100A9, a protein secreted by inflammatory cells, exhibits potent proinflammatory activity. However, its effect on HNE cell remodeling, such as squamous metaplasia, remains unclear. Therefore, this study aimed to determine the effects and underlying pathways of S100A9 on HNE cell remodeling and investigate its clinical implications in chronic rhinosinusitis (CRS). METHODS: Cultured HNE cells were treated with S100A9. Bulk RNA sequencing was performed to analyze gene ontology (GO). Ingenuity pathway analysis (IPA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were also analyzed. Additionally, immunohistochemistry and multiplex immunofluorescence were performed on tissue samples obtained from 60 patients, whose clinical informations were also reviewed. RESULTS: GO enrichment analysis indicated that S100A9 induced tissue remodeling in HNE cells toward squamous metaplasia. IPA and KEGG commonly showed that S100A9 affected HNE cells associated with the IL-17 signaling pathway, including target molecules such as matrix metalloproteinase 1 (MMP1) and small proline-rich protein 2A (SPRR2A). Squamous metaplasia with a marked expression of S100A9 was observed in 50% of CRS with nasal polyps (CRSwNPs). In addition, in multiplex immunofluorescence, the S100A9 in sub-epithelium was co-expressed with myeloperoxidase, a neutrophil marker, and MMP1 and SPRR2A were strongly expressed in epithelial remodeling. Clinically, the expression of S100A9 correlated with sino-nasal outcome test-22 (r = 0.294, p = 0.022) and Lund-Mackay scores (r = 0.348, p = 0.006). CONCLUSION: S100A9 induces tissue remodeling in HNE cells. Its increased expression in CRSwNP, particularly squamous epithelium, correlates with disease severity. This suggests the clinical potential of S100A9 as a biomarker for CRS severity.

Humans↗
PubMed1977

Condylar fractures of the mandible. II. a radiographic study of remodeling processes in the temporomandibular joint.

Remodeling processes in 76 temporomandibular joints were studied on radiographs from 67 individuals sustaining condylar fractures. The indivuduals were ranged into four age groups: 3-11, 12-15, 16-19, and larger than or equal to 20 years of age at the time of fracture. The radiographic examinations were to be performed at the time of the trauma and 3, 6, 12, 24 and 36-48 months after the injury. In the age group 3-11 there was a complete return to normal skeletal relations in 20 of the 27 joints. Joints in teenagers (12-19) did not become normal to the same extent and in adults only minor remodeling was observed. In children the remodeling of the condylar process was extensive but indistinctly outlined. With increasing age there was a shift towards a more distinct apposition of bone on the posterior part of the condylar head visualized as a double contour. This contour first appeared in the late teens. In adults the remodeling processes seemed only to be part of the functional adjustment. Thus, the remodeling processes of the condylar process in a clinical sense may be looked upon as restitutional in children and adjusting or functional in adults. As regards the articular fossa, in children the remodeling processes were first observed as a double contour, of which the new one became more and more distinct, while the original roof gradually disappeared. The final results was a flattened fossa. In adults, a sclerosis of the roof of the fossa was found.

Adolescent↗
PubMed2026

Non-telomeric function deficiency of TERT enhances pressure overload-induced mouse cardiac remodeling by activation of CNBP-mediated THBS3/ITGB1 pathway.

Recent studies show that telomerase reverse transcriptase (TERT) possesses important new biological functions in gene transcription regulation, signal transduction, tumorigenesis, vascular development and mitochondrial DNA protection independent of the maintenance of telomere length. In this study we investigated the role and mechanisms of TERT in regulating the gene expression and signal transduction during pressure overload-induced cardiac remodeling. The first-generation TERT knockout (Tert-/-) and wild-type littermate control (Tert+/+) male mice were subjected to transverse aortic constriction (TAC) surgery to establish a pressure overload-induced cardiac remodeling model. We showed that pressure overload significantly increased TERT expression in the hearts at 8 weeks after TAC, whereas TERT deficiency remarkably exacerbated pressure overload-induced cardiac dysfunction, cardiac hypertrophy and fibrosis, and reduced the survival rate of the mice. In contrast, TERT overexpression reversed phenylephrine (PE)-stimulated cardiomyocyte hypertrophy and fibrosis in neonatal rat ventricular myocytes (NRVMs). Ttranscriptomic and proteomic analyses revealed that extracellular matrix (ECM)-receptor interaction was a key Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway regulated by TERT in hemodynamic overload-induced cardiac remodeling. TERT knockdown greatly enhanced, while TERT overexpression inhibited the activation of the THBS3/ITGB1 signaling pathway, in which transcription factor cellular nucleic acid-binding protein (CNBP) played a pivotal mediating role by interacting with TERT. In conclusion, the non-telomeric function of TERT in gene transcription regulation and signaling transduction plays an important role during pressure overload-induced myocardial remodeling via modulating CNBP-mediated THBS3/ITGB1 signaling pathway, which provides new targets and strategies for the prevention and treatment of pressure overload-induced cardiac remodeling.

Animals↗
PubMed1979

Differences in intracortical bone remodeling in three aboriginal American populations: possible dietary factors.

Cross sections of intracortical bone revealed differences among three early American populations--Eskimo, Arikara, and Pueblo--in the frequency of a form of remodeling called, here, type II. This remodeling appears to occur exclusively within the walls of haversian canals of well-mineralized osteons. The populations are known to have differed in their nutrition. The Eskimo, with a high-protein diet, exhibited the most frequent type II remodeling, whereas the Pueblo, with a low-protein diet, showed the least. Type II remodeling probably reflects the physiological state of the group. Variation in frequency of classic intracortical bone remodeling was not apparent.

Adult↗
PubMed2026

A reproducible computational transcriptomic framework for cell-type-resolved fibroinflammatory-AKT remodeling in human heart failure.

BACKGROUND: Human heart failure involves multicellular transcriptional remodeling, but public transcriptomic studies often remain disconnected from cell-type localization and perturbational interpretation. METHODS: We developed a reproducible computational workflow integrating human left-ventricular bulk transcriptomes, donor-level cell-type pseudobulk results from a human heart-failure single-cell/single-nucleus atlas, external snRNA-seq support, curated module scoring, focused ligand-receptor prioritization and LINCS/L1000 perturbational matching. RESULTS: Cross-cohort analysis identified 14,358 same-direction HF-associated genes, including 1633 replicated HF-up and 785 replicated HF-down genes. Donor-level pseudobulk analysis localized disease remodeling to cardiomyocyte, fibroblast and myeloid compartments. Activated fibroblast and inflammatory myeloid programs defined a fibroinflammatory remodeling axis connected to context-dependent AKT-associated transcriptional shifts. External snRNA-seq support was strongest for fibroblast activation and AKT-associated remodeling, with etiology-dependent heterogeneity across validation resources. L1000FWD screening prioritized safety-aware perturbational hypotheses, including glimepiride and simvastatin as interpretable candidates requiring experimental validation. CONCLUSIONS: This study provides a computational transcriptomic framework linking reproducible human HF signatures, cell-type-resolved fibroinflammatory remodeling and perturbational genomic prioritization without claiming drug efficacy or AKT causality.

Humans↗
PubMed2026

Remodeling of host lipid metabolism by Wolbachia strain wAlbB is associated with lipid accumulation and cardiolipin dysregulation in the Aedes aegypti fat body.

BACKGROUND: The intracellular symbiont Wolbachia, particularly the wAlbB strain, is a promising biocontrol agent against mosquito-borne diseases. Although Wolbachia infection is known to perturb host metabolism, the underlying mechanisms, especially those related to lipid metabolism, remain poorly understood. METHODS: We performed an integrated multi-level analysis of the Aedes aegypti fat body in uninfected and wAlbB-infected mosquitoes, combining histology, biochemistry, untargeted liquid chromatography-mass spectrometry (LC-MS) lipidomics, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis, reverse transcription quantitative PCR of key metabolic genes, and quantification of acetyl-coenzyme A (acetyl-CoA) and reduced nicotinamide adenine dinucleotide (NADH) levels. RESULTS: wAlbB infection increased fat body wet weight and thickness, accompanied by accumulation of triglyceride and of lipid droplets. Lipidomic analysis further revealed extensive lipidome remodeling, with elevated free fatty acid, diglyceride, and triglyceride, but broad depletion of glycerophospholipids, particularly cardiolipin. These changes were supported by transcriptional alterations: upregulation of fatty acid synthase 1 and glycerol-3-phosphate acyltransferase 1, and downregulation of adipose triglyceride lipase and carnitine palmitoyltransferase 1. Cardiolipin depletion correlated with downregulation of genes involved in its synthesis and remodeling, including phosphatidylglycerophosphate synthase and calcium-independent phospholipase A2γ. These lipid changes were also associated with accumulation of acetyl-CoA and NADH. CONCLUSIONS: Our findings suggest that wAlbB infection is associated with extensive lipid metabolic remodeling in the Aedes aegypti fat body, characterized by accumulation of neutral lipids and cardiolipin depletion, accompanied by transcriptional remodeling of key metabolic enzymes. This study establishes the fat body as a primary tissue-level hub for Wolbachia-associated lipid remodeling and provides a foundational framework for future mechanistic investigations into host-symbiont metabolic interactions.

Animals↗
PubMed2009

Nap1-mediated actin remodeling is essential for mammalian myoblast fusion.

Myoblast fusion is crucial for the formation, growth, maintenance and regeneration of healthy skeletal muscle. Unfortunately, the molecular machinery, cell behaviors, and membrane and cytoskeletal remodeling events that govern fusion and myofiber formation remain poorly understood. Using time-lapse imaging approaches on mouse C2C12 myoblasts, we identify discrete and specific molecular events at myoblast membranes during fusion and myotube formation. These events include rearrangement of cell shape from fibroblast to spindle-like morphologies, changes in lamellipodial and filopodial extensions during different periods of differentiation, and changes in membrane alignment and organization during fusion. We find that actin-cytoskeleton remodeling is crucial for these events: pharmacological inhibition of F-actin polymerization leads to decreased lamellipodial and filopodial extensions and to reduced myoblast fusion. Additionally, shRNA-mediated inhibition of Nap1, a member of the WAVE actin-remodeling complex, results in accumulations of F-actin structures at the plasma membrane that are concomitant with a decrease in myoblast fusion. Our data highlight distinct and essential roles for actin cytoskeleton remodeling during mammalian myoblast fusion, provide a platform for cellular and molecular dissection of the fusion process, and suggest a functional conservation of Nap1-regulated actin-cytoskeleton remodeling during myoblast fusion between mammals and Drosophila.

Actins↗
PubMed2026

Integrative dual-track transcriptomics reveals stage-specific coordination, regulatory divergence, and HSP90AA1-associated remodeling in human folliculogenesis.

Human folliculogenesis depends on coordinated yet non-identical developmental remodeling in the oocyte and its surrounding granulosa cells. When these two compartments remain synchronized and when they diverge into lineage-specific regulatory states, however, remains incompletely resolved. Here we performed an integrative dual-track re-analysis of the human RNA-seq dataset GSE107746, modeling oocytes and granulosa cells as distinct but developmentally linked compartments across follicular progression. Analysis of 148 sequencing libraries showed that compartment identity was the dominant source of transcriptomic variation, supporting compartment-aware downstream interpretation. Within this framework, oocytes followed a relatively continuous developmental trajectory, with substantial transcriptional remodeling already evident across adjacent stages, whereas granulosa cells showed weaker early-stage contrasts but markedly stronger late-stage reorganization, particularly around the antral and preovulatory transitions. Functional enrichment indicated that oocyte maturation was associated with RNA-processing and broader genome-regulatory remodeling, whereas granulosa maturation was dominated by progressive mitochondrial and bioenergetic activation. Co-expression analysis showed that both compartments contained strong late-stage programmes together with inverse early-state modules, indicating a shared systems-level architecture of maturation, although the hub-gene composition and biological content of these programmes were largely compartment-specific. Machine-learning validation reinforced this asymmetry: oocyte stage classification was best recovered from a compact eigengene-based representation, whereas granulosa stage discrimination was better resolved by a broader differential-expression-derived feature set. At the gene level, HSP90AA1 emerged as a stage-associated marker with compartment-specific behavior, showing progressive attenuation across oocyte development, assignment to the selected oocyte blue module, and sharper transitional dynamics in granulosa cells. Together, these findings support a model in which human folliculogenesis proceeds through coordinated but non-equivalent transcriptomic remodeling, with shared developmental logic at the systems level but distinct molecular execution in germline and somatic compartments.

Co-expression networks↗
PubMed2026

Nurse-led attribution remodeling training based on the Neuman systems model to enhance resilience, adaptive coping, and attributional style in women newly diagnosed with breast cancer: A randomized controlled trial.

BACKGROUND: Psychological interventions for patients with breast cancer often overlook the critical role of maladaptive attributional style in shaping their adjustment. Therefore, the need for theory-driven, scalable interventions that target cognitive restructuring, particularly during the vulnerable post-diagnosis period, is clear. OBJECTIVE: To evaluate the effectiveness of a nurse-led attribution remodeling training intervention grounded in the Neuman systems model for improving resilience, adaptive coping, and attributional style among women newly diagnosed with breast cancer. DESIGN: A randomized controlled trial. SETTING: A tertiary general hospital. PARTICIPANTS: A total of 130 eligible women newly diagnosed with breast cancer were recruited between March and November 2024. METHODS: A two-arm parallel-group randomized controlled trial was conducted. Participants were randomly assigned to receive either attribution remodeling training plus routine nursing (n = 65) or routine nursing only (n = 65). The nurse-led attribution remodeling training intervention, delivered via a blended model of in-person sessions and continued support through the WeChat mobile platform, was designed to systematically reshape maladaptive attributions into more adaptive ones. Resilience (primary indicator), coping strategy (i.e., confrontation, avoidance, resignation), and attributional style (secondary indicators) were assessed at baseline and at 1, 3, and 6 months post-baseline. A linear mixed model was used to analyze the effects of group, time, and group-by-time interactions. Effect sizes (Cohen's D) were calculated based on the means and standard deviations. RESULTS: At the 6-month follow-up, the intervention group had better outcomes than the control group in terms of resilience (mean difference: 1.49, 95% confidence interval: 0.37, 2.61), confrontation coping (3.35 [2.33, 4.37]), and adaptive attributional style (4.16 [3.87, 4.45]). Avoidance coping showed a small increase (0.82 [0.22, 1.42]), whereas resignation coping decreased (-1.66 [-2.49, -0.83]). Group effects and group-by-time interactions were statistically significant for all outcomes. Effect sizes at 6 months ranged from small for resilience (D = 0.28) and avoidance coping (D = 0.26) to moderate for confrontation coping (D = 0.60) and resignation coping reduction (D = -0.51), and large for attributional style (D = 0.94). CONCLUSIONS: Attribution remodeling training is a promising and effective theory-based intervention that can enhance psychological adaptation in women newly diagnosed with breast cancer. By strengthening key defense mechanisms, as conceptualized by the Neuman systems model, the program is effective, scalable, and nurse-deliverable for psycho-oncology care, bridging a critical gap in supportive cancer care and empowering nurses as primary psychological support providers. REGISTRATION: ChiCTR2000031827, registered prospectively on April 11, 2020, www.Chictr.or.cn.

Humans↗
PubMed2026

Adaptive and degenerative mitochondrial remodeling define distinct redox states in age-related macular degeneration.

Age-related macular degeneration (AMD) is associated with mitochondrial dysfunction and oxidative stress, yet the relationship between mitochondrial remodeling, redox homeostasis, and disease progression remains poorly understood. Nonhuman primates (NHPs) develop spontaneous AMD-related phenotypes, including punctate deposits and soft drusen, providing a unique animal model to investigate mitochondrial pathology in the aging retinal pigment epithelium (RPE). We integrated quantitative mitochondrial ultrastructural profiling with flavoprotein fluorescence imaging, plasma metabolomics, and whole-exome sequencing to characterize mitochondrial and redox alterations in aged rhesus macaques with AMD-related lesions. Flavoprotein fluorescence imaging demonstrated increased metabolic heterogeneity in eyes with soft drusen, consistent with altered mitochondrial redox states and oxidative stress. Morphometric analysis identified distinct mitochondrial remodeling patterns across phenotypes. Normal aging was characterized by concentric cristae and type I paracrystalline inclusions. Eyes with punctate deposits exhibited increased mitochondrial fusion-associated morphology, hyperbranching, and type I paracrystalline inclusions, consistent with a stress-responsive mitochondrial remodeling pattern. In contrast, eyes with soft drusen exhibited reduced fusion-associated morphology, reduced structural complexity, and ultrastructural features consistent with mitochondrial deterioration. These ultrastructural patterns were accompanied by distinct plasma metabolomic signatures. Punctate deposits were associated with altered glycolytic, tricarboxylic acid cycle, and redox-buffering metabolites, consistent with differences in stress-responsive metabolism, whereas soft drusen exhibited metabolomic signatures consistent with altered redox homeostasis. Whole-exome sequencing identified a mitochondrial DNA variant, MT:9582G > A, in cytochrome c oxidase subunit III (COX3) associated with the drusen phenotype. Collectively, these findings identify distinct mitochondrial remodeling patterns associated with AMD-related phenotypes in aged rhesus macaques. The convergence of ultrastructural, imaging, metabolomic, and genetic analyses suggests that punctate deposits and soft drusen are associated with different mitochondrial and redox-related responses to chronic retinal stress. These findings provide a framework for future studies investigating mitochondrial biology and redox-driven mechanisms in AMD.

Animals↗
PubMed2002

Distinct domains of erythroid Krüppel-like factor modulate chromatin remodeling and transactivation at the endogenous beta-globin gene promoter.

Characterization of the mechanism(s) of action of trans-acting factors in higher eukaryotes requires the establishment of cellular models that test their function at endogenous target gene regulatory elements. Erythroid Krüppel-like factor (EKLF) is essential for beta-globin gene transcription. To elucidate the in vivo determinants leading to transcription of the adult beta-globin gene, functional domains of EKLF were examined in the context of chromatin remodeling and transcriptional activation at the endogenous locus. Human EKLF (hEKLF) sequences, linked to an estrogen-responsive domain, were studied with an erythroblast cell line lacking endogenous EKLF expression (J2eDeltaeklf). J2eDeltaeklf cells transduced with hEKLF demonstrated a dose-dependent rescue of beta-globin transcription in the presence of inducing ligand. Further analysis using a series of amino-terminal truncation mutants of hEKLF identified a distinct internal domain, which is sufficient for transactivation. Interestingly, studies of the chromatin structure of the beta-promoter revealed that a smaller carboxy-terminal domain generated an open promoter configuration. In vitro and in vivo binding studies demonstrated that this region interacted with BRG1, a component of the SWI/SNF chromatin remodeling complex. However, further study revealed that BRG1 interacted with an even smaller domain of EKLF, suggesting that additional protein interactions are required for chromatin remodeling at the endogenous beta-promoter. Taken together, our findings support a stepwise process of chromatin remodeling and coactivator recruitment to the beta-globin promoter in vivo. The J2eDeltaeklf inducible hEKLF system will be a valuable tool for further characterizing the temporal series of events required for endogenous beta-globin gene transcription.

Animals↗
PubMed2026

Early Cardiomyopathy in Prediabetic NDPK-B-Deficient Mice Is Associated with Remodeling of the Mitochondrial O-GlcNAc Proteome.

Diabetic cardiomyopathy (DCM) is characterized by myocardial remodeling that may already be evident during prediabetes, yet the molecular alterations accompanying these early changes remain poorly understood. The present study examined mouse models of Nucleoside diphosphate kinase B (NDPK-B)-deficient prediabetes and streptozotocin-induced diabetes using O-GlcNAc-associated proteomic profiling to define stage-specific molecular alterations during the progression from prediabetic to diabetic cardiomyopathy. Both models exhibited increased left ventricular extracellular matrix deposition and impaired diastolic function, together with activation of the hexosamine biosynthesis pathway. Profiling of O-GlcNAc-associated proteins uncovered extensive remodeling of the mitochondrial proteome already at the prediabetic stage, with respiratory complex I among the most prominently altered targets, alongside changes in substrate metabolism and inflammatory signaling. In overt DCM, the putative O-GlcNAc proteomic profile was associated with a shift toward wider lipid-dependent metabolic reprogramming and remodeling of mitochondrial proteins. These findings identify early remodeling of the mitochondrial O-GlcNAc-associated proteome as a molecular signature of prediabetic cardiomyopathy and highlight respiratory complex I proteins as candidate targets for future mechanistic investigations.

Animals↗
PubMed1977

Comparative study of healing and remodeling in various bones.

The effects of normal physiologic stimuli on healing and remodeling in various bones of different embryogenic origin in the rabbit and dog were compared. The findings disclosed that the healing and remodeling of the tibia and mandible were consistent with the magnitude of the forces that act on these bones; namely, the tension created by muscle contraction and the compression exerted by body weight in the tibia, and masticatory compression in the mandible. The slower healing and remodeling in the maxilla was attributed to the selection of the excision of bone in the edentulous site with minimal masticatory compression and muscle-pull tension. The excision of the bone in the skull appeared to heal by fibrous tissue with no evidence of remodeling, which is consistent with the minimal external forces that act on this bone.

Animals↗
PubMed2026

LncRNA H19 promotes vascular remodeling by inhibiting MFN2.

Neointimal hyperplasia, featuring excessive proliferation and migration of vascular smooth muscle cells (VSMCs), is crucial in vascular remodeling diseases. Long non-coding RNA (lncRNA) H19 promotes vascular remodeling, yet underlying mechanisms remain incompletely elucidated. Here, we investigated whether H19 acts via its derivative miR-675-5p. Bioinformatics found a conserved H19/miR-675-5p/MFN2 (mitofusin 2) axis. Cell assays were performed to evaluate the effects of H19 and miR-675-5p on VSMC proliferation and migration. The dual-luciferase reporter gene assay was used to assess the interaction between miR-675-5p and Mfn2 mRNA. The mouse model of common carotid artery ligation was used to evaluate the role of H19 in neointimal hyperplasia. Our data suggested that knockdown of H19 inhibited VSMC proliferation and migration, as well as neointimal hyperplasia. Mechanistically, H19 regulated MFN2 through miR-675-5p, leading to ERK1/2 (extracellular signal-regulated kinase 1/2) activation. In conclusion, we suggest that targeting the H19/miR-675-5p/MFN2/ERK1/2 axis may help to treat vascular remodeling diseases.

Animals↗
PubMed2025

The impact of m6A methyltransferase METTL3 on airway remodeling in bronchial asthma.

BACKGROUND: Methyltransferase-like 3 (METTL3) is known to play a role in asthma airway remodeling and cell proliferation. Adenylate kinase 4 (AK4) regulates the proliferation of pulmonary artery smooth muscle cells and exerts its effects through the protein kinase B (AKT) pathway. However, the role of METTL3 and AK4-AKT in bronchial smooth muscle cells remains unclear. METHODS: Systemic METTL3 knockout mice and a mouse model of asthma were established. Airway remodeling was assessed using pulmonary function tests, histopathological staining, and Western blot analysis. RNA sequencing (RNA-seq) was performed to detect changes in gene expression following METTL3 knockdown. The 5-ethynyl-2'-deoxyuridine (EdU) assay was used to evaluate cell proliferation. Finally, the expression levels of relevant proteins were validated by Western blotting. RESULTS: Compared with the control model group, the METTL3 knockout group showed significantly reduced inflammatory cell infiltration, decreased collagen fiber deposition, and attenuated airway smooth muscle hyperplasia. RNA-seq revealed that the expression of numerous proliferation-related genes, including AK4, was upregulated following METTL3 knockdown. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that these genes were primarily enriched in the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway. The EdU assay demonstrated that METTL3 knockdown inhibited cell proliferation. Western blot validation showed increased AK4 expression in lung tissues of the METTL3 knockout group compared to the control group, while phosphorylated AKT (p-AKT) levels were reduced. CONCLUSIONS: METTL3 knockout inhibits airway smooth muscle hyperplasia and alleviates airway remodeling in asthma. This effect may be mediated through the regulation of AK4 and the AKT signaling pathway.

Airway Remodeling↗
PubMed2026

Glycerophospholipid remodeling under osmotic stress in grass carp gills.

Salinity fluctuations represent a pervasive environmental challenge for freshwater fishes, yet the cellular and metabolic programs governing early osmoregulatory responses remain understudied. Here, we investigated the time-dependent gill responses of juvenile grass carp (Ctenopharyngodon idella) subjected to an acute, sublethal salinity increase 9 parts per thousand (ppt). Histological and biochemical analyses revealed progressive gill lesions accompanied by elevated lactate dehydrogenase (LDH) activity and lipid peroxidation, indicating rapid tissue injury under osmotic stress. Integrative metabolomic and transcriptomic profiling uncovered pronounced temporal reprogramming, consistently highlighting glycerophospholipid metabolism as a central axis of response. In particular, phosphatidylcholine (PC) species exhibited dynamic remodeling, coupled with transcriptional enrichment of lipid turnover, membrane transport, and innate immune pathways. Network-based integration identified a PC-centered remodeling module characterized by accelerated PC headgroup turnover, disruption of the PLA2-LPCAT2 lyso-PC reacylation cycle, and enhanced ABC transporter-associated lipid and sterol export, reflected by cholesteryl sulfate accumulation and a shifted n-6 polyunsaturated fatty acid-derived oxylipin signature. Functional assays further demonstrated that PC and linoleic acid (LA) supplementation improved cell viability and alleviated oxidative stress and pro-inflammatory signaling in grass carp cells under salinity challenge. Collectively, these findings reveal phospholipid-centered membrane remodeling as an early, integrative mechanism linking osmotic stress to gill injury and immune activation in freshwater fish, providing insights into potential strategies of environmental stress adaptation.

Animals↗