Cell Proliferation最新文献

Advancements in the generation of human pluripotent stem cell-derived natural killer (PSC-NK) cells have attracted considerable attention within the biomedical research community, offering a promising off-the-shelf technique for universal immune therapy. However, this technique is associated with certain ethical, safety, and regulatory challenges, including ensuring genomic stability, preventing contamination and adhering to rigorous ethical standards for cell sourcing and obtaining informed consent. Addressing these challenges would require robust quality control, transparent data-sharing practices, and cross-border collaboration to ensure alignment with ethical and scientific standards. Future development must therefore focus on patient safety, data privacy and equitable access within a comprehensive ethical framework. These measures are crucial for maintaining public trust in and enabling the responsible clinical integration of PSC-NK therapies, thereby supporting their advancement while maintaining a balance between innovation and societal and ethical considerations.

The normal growth and development of skeletal muscle are crucial for the proper function of organisms. During myoblast development, cell death is a fundamental physiological process, and skeletal muscle damage involves various types of cell death, including ferroptosis. However, ferroptosis-related biomarkers in skeletal muscle damage remain unclear. This study aimed to investigate the mechanisms by which lipocalin-2 (LCN2), a key protein of iron metabolism, regulates skeletal muscle regeneration post damage by mediating ferroptosis. When the gastrocnemius muscle (GAS) of mice is acutely injured, LCN2 is significantly upregulated early in the injury. In vitro, LCN2 participates in the inhibition of proliferation and differentiation of C2C12 cells via erastin-induced ferroptosis. Transcriptomic analysis after the overexpression of LCN2 revealed that the one with the most significant difference among all of the differentially expressed genes (DEGs) was aconitate decarboxylase 1 (Acod1). The inhibition of myogenic factors' expression by LCN2 was associated with the activation of the ferroptosis signalling pathway, partly attributed to the mitochondrial dysfunction. The ACOD1 inhibitor attenuated mitochondria-associated ferroptosis induced by LCN2 and alleviated the inhibitory effect of LCN2 on cell viability. These findings highlight the therapeutic potential of targeting the LCN2-ACOD1 signalling to promote myogenesis, providing promising strategies for facilitating the regeneration of skeletal muscle after injury and the treatment of muscle-related diseases.

The malignant transformation of cancer cells is underpinned by the dysregulation of essential cellular processes, including genome stability maintenance, DNA repair, transcriptional control and signal transduction. These processes are not randomly distributed but are spatiotemporally coordinated through dynamic molecular assemblies. Recent advances have highlighted the pivotal role of biomolecular condensates, membraneless compartments formed via liquid-liquid phase separation (LLPS), in compartmentalising and regulating these key functions. LLPS enables the concentration and organisation of proteins and nucleic acids, creating distinct biochemical environments that facilitate cellular decision-making. Importantly, aberrant phase separation has been increasingly implicated in the acquisition of cancer hallmarks, such as sustained proliferative signalling, resistance to cell death and immune evasion. In this review, we summarise the physicochemical principles of LLPS, examine its emerging roles in oncogenic transformation and discuss the therapeutic potential of targeting phase separation in cancer. Our findings highlight LLPS as a novel and versatile regulatory layer in tumour biology and an emerging frontier in precision oncology.

Targeting macrophage SCTR mitigates integrated profibrotic, inflammatory, ER stress, and senescent pathways, preserving lung function and revealing a novel therapeutic strategy for silicosis.

Adeno-associated virus (AAV) has emerged as the predominant viral vector in clinical gene therapy. However, its widespread application confronts critical challenges, including pre-existing neutralising antibodies in 40%-80% of the population, species-dependent therapeutic discrepancies, and suboptimal tropism specificity. While current AAV capsid modification strategies (e.g., directed evolution and rational design) have advanced the field, their implementation has been hampered by incomplete mechanistic understanding and persistent translational roadblocks, necessitating the need for the discovery of novel AAV capsids. In this study, we systematically captured 1925 natural AAV variants from non-human primate (NHP) tissues by integrating multiple Polymerase Chain Reaction (PCR) primers and deep long-read sequencing technology, significantly expanding the natural capsid library by more than 20-fold and identifying 1274 representative AAV11 family variants. Based on the co-evolution analysis of these natural AAV11 variants, we designed the engineered variant AAV11.P5V6, which showed significantly enhanced transduction efficiency in human and NHP primary hepatocytes in vitro and achieved efficient targeting in a mouse central nervous system model. In addition, AAV11 and its variants maintain a strong antibody escape ability in human serum and immune animal models, exhibiting unique serological characteristics with almost no cross-neutralisation reaction with AAV8 and AAV9, confirming its low serum prevalence and immune evasion advantages. This study established a systematic framework of 'natural discovery-evolutionary analysis-functional optimization', providing a new paradigm for the development of next-generation AAV vectors with clinical-grade tissue specificity, low immunogenicity, and cross-species compatibility.

Breast cancer remains the most prevalent malignancy among women, and radiotherapy plays a pivotal role in reducing local recurrence and improving prognosis. However, the emergence of radioresistance in a subset of patients significantly compromises treatment efficacy, underscoring the need for a deeper understanding of the underlying molecular mechanisms. In recent years, non-coding RNAs (ncRNAs) have emerged as key regulators of gene expression and have garnered increasing attention for their roles in mediating radioresistance in breast cancer. This review systematically summarises the major molecular mechanisms by which ncRNAs contribute to breast cancer radioresistance, including cell cycle regulation, DNA damage repair, programmed cell death (e.g., apoptosis, autophagy and ferroptosis), oxidative stress response, tumour microenvironment remodelling and maintenance of cancer stem cell properties. On the translational front, RNA-based therapeutic approaches-including antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), miRNA mimics and CRISPR/Cas9-offer promising avenues for radiosensitisation, yet face substantial clinical hurdles. These include immune activation, poor delivery specificity, intracellular trafficking barriers and limited stability. Advances in chemical modifications and nanoparticle-based delivery systems-such as redox-responsive nanocarriers-have shown potential in enhancing the efficacy and safety of ncRNA-targeted therapies. Despite encouraging progress, clinical translation remains constrained by a lack of methodological standardisation, insufficient high-quality clinical data, limited biomarker reliability, suboptimal target selection and unresolved safety concerns. Future efforts should prioritise optimisation of delivery platforms, validation of multi-ncRNA biomarker panels in large, multicentre cohorts and integration of multi-omics data to reconstruct comprehensive regulatory networks, ultimately accelerating the clinical deployment of ncRNA-based radiosensitisation strategies.

The mature mammalian heart has limited ability for self-repair and regeneration. Here, we establish phosphoglycerate dehydrogenase (PHGDH) as a crucial key for cardiomyocyte proliferation, with diminishing expression during postnatal cardiac development. PHGDH overexpression promoted myocardial regeneration and cardiac function in apical resection-operated mice, whereas inhibition by NCT-503 inhibited these processes. In vitro, PHGDH stimulated the proliferation of cardiomyocytes (CMs), while NCT-503 abolished its effect. Mechanistically, PHGDH activated the cell cycle and TGF-β/Smad signalling. Moreover, PHGDH significantly enhances cardiac repair and stimulates cardiomyocyte proliferation in adult mice following myocardial infarction. Our study demonstrates that upregulating PHGDH promotes CM proliferation and myocardial regeneration, offering a promising therapeutic target for myocardial repair.

S.-B. Jeon, A.-R. Han, S. Lee, S. C. Lee, M. J. Lee, S.-J. Park, S.-H. Moon, and J. Y. Lee, “CD34dim Cells Identified as Pluripotent Stem Cell-Derived Definitive Hemogenic Endothelium Purified Using Bone Morphogenetic Protein 4,” Cell Proliferation 56, no. 2 (2023): e13366, https://doi.org/10.1111/cpr.13366.

The image depicting erythroblasts in Figure 5C was incorrect and was inadvertently duplicated in two related articles by the same author group. The correct image, corresponding to the erythroblasts used in the separation of hemogenic endothelium cells experiment, is shown below. The authors confirm that all experimental results and corresponding conclusions presented in the paper remain entirely unaffected. The authors sincerely apologise for this error.

The cover image is based on the article Deciphering Age-Dependent ECM Remodelling in Liver: Proteomic Profiling and Its Implications for Aging and Therapeutic Targets by Juan Liu et al., https://doi.org/10.1111/cpr.70087.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a severe complication in patients undergoing long-term bisphosphonate therapy, while our knowledge on the pathogenesis of BRONJ is far from sufficient. Gamma delta (γδ) T cells predominantly distribute in mucosal tissues and play an important role in both immune modulation and bone metabolism; however, the mechanism of γδ T cells in the pathogenesis of BRONJ has not been elucidated. Here, we induced BRONJ-like lesions in wild-type (WT) and T-cell receptor delta-deficient (TCRδ^-/-) mice via intraperitoneal zoledronate injection. Our findings revealed that γδ T cells infiltrating BRONJ lesions suppressed osteoblast differentiation, whereas γδ T cell depletion in TCRδ^-/- mice restored osteogenic function and significantly reduced BRONJ lesion incidence. Mechanistically, we identified matrix metalloproteinase 3 (MMP3) secreted by activated γδ T cells as a critical enzyme cleaving membrane-bound Sema4D (mSema4D) into soluble Sema4D (sSema4D). This cleavage product bound to Plexin-B1/2 receptors on osteoblasts, activating the mTOR signalling pathway to inhibit osteogenic differentiation (ALP/Runx2 downregulation). To promote the repair of BRONJ lesions, we engineered a dual-functional composite hydrogel (Gel-BG@ab) combining PLGA-PEG-PLGA with mesoporous bioactive glass (BG) and anti-Sema4D antibodies. This composite hydrogel achieved sustained antibody release, effectively neutralising sSema4D, restoring osteoblast activity and reducing the formation of BRONJ-like lesions in vivo. This study provides evidence of MMP3-Sema4D-Plexin-B1/2/mTOR crosstalk in BRONJ and introduces a targeted biomaterial strategy to disrupt pathogenic feedback loops. The Gel-BG@ab is the integration of immunomodulation and regenerative medicine, providing both theoretical and technical insights for the immune-material combination therapy of BRONJ.