Cell Proliferation最新文献

ARPC1B⁺ cancer stem cells (CSCs) in pancreatic cancer are identified as a subpopulation resistant to gemcitabine. In our study, drug repositioning, molecular docking, and surface plasmon resonance (SPR) technique jointly revealed that CK-636 can directly target ARPC1B protein with high affinity. In vitro cytotoxicity, ex vivo organoid cultures, in vivo xenograft and orthotopic gemcitabine-resistant pancreatic cancer model demonstrated that combination therapy of gemcitabine plus CK-636 showed a superior anti-tumor effect compared with gemcitabine monotherapy. Our study demonstrated that CK-636 can act as a rational adjuvant to overcome gemcitabine resistance in pancreatic cancer therapy.

Y. Peng, R.-P. Xiong, Z.-H. Zhang, Y.-L. Ning, Y. Zhao, S.-W. Tan, Y.-G. Zhou, and P. Li, “Ski Promotes Proliferation and Inhibits Apoptosis in Fibroblasts Under High-Glucose Conditions via the FoxO1 Pathway,” Cell Proliferation 54 (2021): e12971, https://doi.org/10.1111/cpr.12971.

The corrections do not affect the results or overall conclusions of the study. We apologise for these errors.

Progressive non-alcoholic fatty liver disease (NAFLD) may culminate in severe complications, including fibrosis, cirrhosis and hepatocellular carcinoma, yet therapeutic breakthroughs remain elusive, necessitating novel pharmacological strategies. Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist clinically approved for type 2 diabetes and obesity management, has demonstrated pleiotropic effects in preclinical NAFLD models. In this study, we investigated semaglutide's therapeutic efficacy and mechanisms in a human liver organoids (hLOs) model of NAFLD. Utilising microengineered array chips, human induced pluripotent stem cells (hiPSCs) were differentiated into hLOs with functional hepatic properties. NAFLD pathology was induced via free fatty acid (FFA) exposure, recapitulating disease hallmarks such as steatosis, inflammatory cytokine elevation and fibrogenic activation. Semaglutide treatment at 50 nM significantly attenuated lipid deposition caused by FFAs and reduced triglyceride levels by 8-fold and cholesterol levels by 1.8-fold. It also inhibited the expression of pro-inflammatory markers (IL-6, IL-8, TNF-α) by about 1.5-2 fold and increased the level of lipolytic genes by about 45%. These findings elucidate the therapeutic potential of semaglutide in attenuating key NAFLD-associated pathologies and establish a robust in vitro platform for preclinical drug evaluation. The study provides critical insights into targeted NAFLD interventions and supports the translation of GLP-1-based therapies into clinical practice, addressing an unmet need in hepatology.

Macrophages and bone marrow mesenchymal stem cells (BMSCs) share a close relationship within the osteoimmune microenvironment. During mechanically induced bone formation, macrophages respond to stimuli and regulate this microenvironment, influencing BMSCs' proliferation and differentiation. However, the underlying mechanisms remain incompletely understood. In our study, we employed a cellular tension system and found that mechanical tension altered mitochondrial dynamics in macrophages, leading to increased mitochondrial fission. Using a macrophage-BMSC direct co-culture system, we demonstrated that macrophages transferred mitochondria to BMSCs, a process enhanced by tension. This enhancement was associated with Drp1-mediated mitochondrial fission, as Drp1 knockdown in macrophages abolished the effect. Additionally, using in vitro co-culture and in vivo tibial injection models, we found that mitochondria-rich extracellular vesicles (Mito-EVs) secreted by mechanically stretched macrophages promoted BMSCs' osteogenesis and enhanced bone formation via the CD200 receptor (CD200R)-CD200 interaction. Our findings reveal a pivotal role for mitochondrial transfer in promoting osteogenesis during mechanotransduction, highlighting a novel mechanism of intercellular communication in bone biology.

H1N1, a globally pervasive subtype of influenza A virus (IAV), poses an ongoing threat to human health and occasionally leads to multi-organ dysfunction in severe cases. Evidence confirms that the H1N1 virus is enabled to penetrate the placental barrier; however, the underlying mechanisms by which maternal infection contributes to detrimental fetal outcomes remain elusive. In this study, a systematic literature review and meta-analysis demonstrated a strong association between maternal H1N1 infection during pregnancy and adverse fetal outcomes. Using a chicken embryo model, we found that the H1N1 virus specifically targets the developing liver and lung tissues, activates immune and stromal cells, and induces localised inflammatory responses, thereby triggering excessive oxidative stress. The resulting imbalance in oxidative stress disrupts antioxidant defence systems and promotes ferroptosis in parenchymal cells. Persistent ferroptosis subsequently initiates tissue repair processes, activates fibroblasts, and leads to aberrant extracellular matrix deposition, ultimately contributing to early fibrosis in the liver and lung tissues. Collectively, this study elucidates the molecular mechanisms by which H1N1 selectively infects fetal liver and lung, inducing ferroptosis-mediated parenchymal cell death and tissue fibrosis, thereby impairing fetal development. These findings provide novel theoretical insights for the clinical management and prevention of H1N1-associated maternal-fetal infections and adverse pregnancy outcomes.

Roles of primary cilia and the signals they transmit in the development of myocardial fibrogenesis, cardiac hypertrophy, and atrial fibrillation. Left, Fibroblasts can differentiate into myofibroblasts in response to TGF-β1. TGF-β1 stimulation via both paracrine action in the heart and exogenous action on primary cultured fibroblasts activated the phosphorylation of SMAD3 and the transcription of the fibronectin and collagen type I and III genes. Middle, Vesicles derived from cilia are secreted at an accelerated rate under fluid shear stress. Blockage of ciliary protein, which is required for cELV generation with shRNA, led to blunted cELV secretion and left ventricular hypertrophy. Right, under pathological conditions such as atrial fibrillation (AF), fibroblasts exhibit increased proliferation and differentiation into α-smooth muscle Actin (αSMA)-expressing myofibroblasts. This disrupts ECM dynamics, ultimately leading to interstitial fibrosis within the atria. AF patients presented increased HDAC6 activity and reduced levels of acetylated α-tubulin in left atrial tissues. HDAC6 activity is activated by the interaction of aurora kinase A (AURKA), and neural precursor cells express developmentally downregulated protein 9 (NEDD9) via phosphorylation. LiCl prompts the reversion of αSMA-positive myofibroblasts into αSMA-negative fibroblasts.

Sarcopenia profoundly impacts the quality of life and longevity in elderly populations. Notably, alterations in thyroid hormone (TH) levels during ageing are intricately linked to the development of sarcopenia. In skeletal muscle, the primary action of TH is mediated through the thyroid hormone receptor alpha (TRα). Emerging evidence suggests that decreased TRα expression may precipitate mitochondrial dysfunction in ageing skeletal muscle tissues. Yet, the precise mechanisms and the potential causative role of TRα deficiency in sarcopenia are not fully understood. This study suggests that TRα may regulate mitochondrial calcium (Ca²⁺) transport across membranes by targeting the inositol 1,4,5-trisphosphate receptor 1 (IP3R1), as evidenced by ChIP-seq and RNA-seq analyses. Experiments using naturally aged mice, skeletal muscle-specific TRα knockout (SKT) mice, and C2C12 myoblasts were conducted to investigate this process further. Findings include increased IP3R1, mitochondria-associated endoplasmic reticulum membranes (MAM), and mitochondrial Ca²⁺ in aged skeletal muscle. Additionally, SKT mice exhibited smaller muscle fibres, increased IP3R1 and MAM, and mitochondrial dysfunction. ChIP-qPCR and TRα manipulation in C2C12 cells showed that TRα negatively regulates IP3R1 transcription. Moreover, TRα knockdown cells exhibited increased Ca²⁺ transfer in MAM and mitochondrial dysfunction, which was ameliorated by the IP3R1 inhibitor 2-aminoethoxydiphenyl borate. Reintroduction of TRα improved IP3R1-mediated mitochondrial Ca²⁺ overload in aged cells. Our findings uncover a novel mechanism by which TRα deficiency induces mitochondrial Ca²⁺ overload through IP3R1-mediated Ca²⁺ transfer in MAM, exacerbating skeletal muscle atrophy during ageing. The TRα/IP3R1 pathway in MAM Ca²⁺ transfer presents a potential therapeutic target for sarcopenia.

X. Wu, W. Zhao, H. Wu, Q. Zhang, Y. Wang, K. Yu, J. Zhai, F. Mo, M. Wang, S. Li, X. Zhu, X. Liang, B. Hu, G. H. Liu, J. Wu, H. Wang, F. Guo, and L. Yu, “An Aggregation of Human Embryonic and Trophoblast Stem Cells Reveals the Role of Trophectoderm on Epiblast Differentiation,” Cell Proliferation 56, no. 5 (2023 May): e13492, https://doi.org/10.1111/cpr.13492.

In the originally published version of this article, Figure 4E contained an unintended duplication error. Specifically, the left and right panels were mistakenly presented as identical due to a manual error during figure reformatting. This occurred while the figure was being adjusted for higher resolution.

We apologize for this error.

PE is a life-threatening pregnancy disorder that can lead to adverse events for both the fetus and the mother. Autophagy is a cellular process involved in cellular renovation and maintaining homeostasis. There is a growing body of evidence suggesting that autophagy in trophoblasts plays a significant role in the development and pathogenesis of PE. However, the exact mechanisms are not yet fully understood. This article provides an overview of recent evidence regarding the role of autophagy in trophoblast invasion, vascular remodelling, inflammation, immune response, and maternal factors in the context of PE. It is believed that impaired or excessive autophagy can contribute to placental ischaemia and hypoxia, thereby exacerbating PE progression. Therefore, understanding the molecular mechanisms that regulate autophagy in PE is crucial for the development of targeted therapeutic interventions in the future.