Cell Proliferation最新文献

Sleep deprivation (SD) is a common issue among pregnant women. Maternal SD led to adverse effects on offspring health such as cognitive impairment through dysregulated metabolic pathways. However, it remains unknown whether maternal SD increases the offspring's susceptibility to nonalcoholic steatohepatitis (NASH) development. Here, we induced maternal SD during pregnancy and observed that maternal SD during pregnancy promoted the development of diet-induced NASH in offspring of both sexes in adulthood, with exacerbation of liver weight gain, hepatic steatosis, fibrosis, and hepatic dysfunction. The primary hepatocytes isolated from SD offspring were also more susceptible to palmitate acid-induced lipotoxic injury. Mechanistically, the detrimental effects of maternal SD were associated with augmented activation of inflammatory and apoptosis pathways in offspring liver tissues, which were attributed to upregulation of the transcription factor nuclear receptor subfamily 4 group A member 3 (NR4A3). The melatonin signalling is reported to be pivotally affected by sleep disturbance both at the circulation and the placenta, and our further analysis revealed that melatonin supplementation during maternal SD normalised NR4A3 expression in offspring liver and alleviated the increased steatohepatitis susceptibility in offspring. Taken together, these results suggest that maternal SD during pregnancy predisposes offspring to NASH development in adulthood via an NR4A3-dependent mechanism, and maternal melatonin supplementation may hold promise for improving liver health in the offspring.

Regeneration of the central nervous system (CNS) is a complex and tightly regulated process, yet the precise molecular players and transcriptional regulators involved remain incompletely understood. Here, we identify Host Cell Factor-1 (Hcfc1), a transcriptional co-regulator, and O-GlcNAc transferase (Ogt), which cleaves and O-GlcNAcylates HCF-1, as crucial regulators of zebrafish brain and retinal regeneration. We uncover their interplay with the Hippo/Yap signalling pathway, a well-known regulator of tissue growth and repair. Knockdown of hcfc1a/b or Ogt activity inhibition disrupts regeneration and reduces Yap levels, while Yap inhibition alone also impairs regeneration. Strikingly, overexpression of constitutively active Yap5SA rescues proliferation defects caused by Hcfc1 depletion and Ogt inhibition in retinal regeneration. Further, yap1 knockdown reduces hcfc1a/b levels, suggesting potential feedback regulation. These findings reveal a previously unrecognised regulatory axis involving Hcfc1, Ogt, and the Hippo/Yap pathway, which governs CNS regeneration. Targeting this pathway could offer a strategy for enhancing CNS regeneration.

Pulmonary vascular endothelial cells (VECs) are essential for the normal function of the lung, through maintaining vascular barrier integrity, regulating blood flow, and participating in inflammatory responses to safeguard oxygen exchange and physiological homeostasis. The occurrence and development of various pulmonary diseases all take the injury of pulmonary VECs as an important pathological hub, which directly affects the therapeutic effect and prognosis recovery of patients. The injury mechanisms of pulmonary VECs present multi-dimensional network characteristics, involving inflammation and oxidative stress, genetic factors, cellular senescence, metabolic abnormalities, and immune dysregulation. Due to the unique physiological structure of the lungs, traditional drugs often encounter significant challenges in clinical application such as insufficient targeting, low bioavailability, and systemic side effects. In order to overcome the existing treatment bottlenecks, it is crucial to implement an in-depth analysis of the molecular mechanism of pulmonary VECs injury. This review systematically explores the mechanisms of pulmonary VECs injury, evaluates novel therapeutic strategies targeting pulmonary VECs' dysfunction, and discusses the challenges and future prospects of clinical translation. The goal is to shift pulmonary diseases treatment from symptom management to precise molecular intervention.

Luteolin alleviates DSS-induced ulcerative colitis in mice by targeting the NLRP3 inflammasome, as it shows no effect in NLRP3^-/- mice. It inhibits NLRP3 activation and IL-1β secretion in macrophages by reducing ROS, mtROS and calcium levels via AMPK binding and signalling. Metabolomic changes suggest lipid metabolism involvement. Luteolin represents a promising NLRP3-targeted therapeutic candidate for UC.

Open skin wounds caused by burns, trauma, or underlying diseases impose substantial clinical challenges and significantly compromise patients' quality of life due to their complex management and high risk of scarring. In this study, we explore the therapeutic potential of apoptotic vesicles derived from interleukin-10-treated fibroblasts (IL10_ApoEVs) in promoting cutaneous wound healing and mitigating fibrotic scar formation. Our results demonstrate that IL10_ApoEVs enhance mitochondrial function and oxidative phosphorylation (OXPHOS), while concurrently suppressing glycolytic activity in fibroblasts. Importantly, IL10_ApoEVs markedly inhibit the Hedgehog signalling pathway, a key driver of fibrogenesis in various tissues, as evidenced by the downregulation of Shh and Gli1 expression. This modulation leads to attenuated aberrant extracellular matrix (ECM) deposition and promotes a favourable shift in collagen composition. This is characterized by increased type III collagen and reduced type I collagen, which is indicative of more elastic and functionally integrated tissue remodelling. These findings suggest that IL10_ApoEVs contribute to a regenerative microenvironment that supports scarless or minimally fibrotic healing. Collectively, our work highlights the promising application of IL10_ApoEVs in regenerative medicine and provides mechanistic insights into their dual role in metabolic reprogramming and antifibrotic signalling modulation during tissue repair.

The cover image is based on the article Lactate Promotes the Second Cell Fate Decision in Blastocysts by Prompting Primitive Endoderm Formation Through an Intercellular Positive Feedback Loop That Couples Paracrine FGF Signalling by Xiao Hu et al., https://doi.org/10.1111/cpr.70088.

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.