Cell Cycle最新文献

Adipose tissue is central to energy homeostasis and endocrine function, and its dysregulation is a key driver of metabolic disorders. Exosomes, serving as critical intercellular messengers, mediate systemic metabolic responses by delivering bioactive cargo, including nucleic acids, proteins, and lipids. Mounting evidence identifies adipose-derived exosomes as potent mediators of obesity-related inflammation and glucose metabolic dysfunction, thereby contributing to insulin resistance and diabetic complications. This review summarizes the pivotal roles of exosomal microRNAs (miRNAs) and highlights their significant potential as a novel class of small RNA therapeutics. Unlike synthetic delivery systems, exosomal miRNAs constitute an inherent delivery vehicle that synergizes natural targeting efficiency with potent gene regulatory functions. This unique combination enables the precise coordination of complex gene networks involved in metabolic disease, offering a distinct advantage over conventional single-target approaches. Consequently, exosomal miRNAs are positioned as promising candidates for pioneering RNA-based therapies against pervasive conditions such as diabetes and cardiovascular disease.

Glioma has long been a threat to human health and new treatments are required to address this health problem. We here explored the potential use of benzbromarone as a supplement to existing chemotherapy strategies. The effects of benzbromarone on the proliferation and migration of C6 glioma cells were evaluated by MTT and wound healing assays. The effects of benzbromarone on cell cycle arrest and apoptosis in C6 glioma cells were determined by flow cytometry. The effect of benzbromarone on reactive oxygen species (ROS) production was determined through fluorescence microscopy and flow cytometry. Finally, the effect of benzbromarone on the NF-κB pathway was determined by western blotting and immunofluorescence. Benzbromarone inhibited the growth and migration of C6 glioma cells in a concentration-dependent manner. Benzbromarone also induced cell cycle arrest and apoptosis in C6 glioma cells, in addition to increasing ROS generation. Western blot analysis revealed that benzbromarone activated the NF-κB signaling pathway. Our results suggest that benzbromarone induces cytotoxicity through ROS production. These findings indicate the potential of benzbromarone as a treatment of glioma.

Insulin resistance (IR) is the main feature of type 2 diabetes mellitus. Furthermore, viral infection can aggravate the abnormal glucose metabolism in diabetic patients. GABBR1 can maintain normal glucose homeostasis, but its specific role in diabetes is not clear. We investigated the function of the GABBR1/miR-19b-3p/WNT2B axis in vitro and in vivo. miR-19b-3p and GABBR1 were overexpressed or knocked down in AML12 cells. Subsequently, these cells were treated with palmitic acid (PA) to induce damage or poly I : C to mimic viral infection. The degree of AML12 cell damage was assessed using the CCK-8 assay; inflammation levels were measured using ELISA; and IR indexes were determined using the Immunofluorescence kit and Western blot assay. The diabetic mice model was established to evaluate liver injury and IR. PA and poly I : C can reduce the activity of AML12 cells, increase apoptosis and inflammatory factor contents, weaken the ability of glucose uptake and consumption, enhance the production capacity, and reduce the level of GLUT4. GABBR1 mediates the targeted regulation of WNT2B by miR-19b-3p. PA and poly I : C also increased ALT, AST, inflammatory factors and miR-19b-3p levels, and decreased GABBR1 and WNT2B expression of mice. Liver cells showed swelling and many spherical lipid droplets. After miR-19b-3p knockdown and GABBR1 overexpression, the degree of liver injury and IR in AML12 cells and mice were alleviated. GABBR1 regulates miR-19b-3p/WNT2B axis to reduce liver injury, IR and inflammatory response, and improve the comorbidity of diabetes and viral infection. This pathway represents a potential therapeutic target for mitigating the comorbidity of diabetes and viral infection.

Mutations in ATP8B1 cause a spectrum of cholestatic liver disease, ranging from Progressive-Familial-Intrahepatic-Cholestasis type-1 (PFIC1) to Benign-Recurrent-Intrahepatic-Cholestasis type-1 (BRIC1). Manifestations of PFIC1 include severe pruritus, jaundice, and liver damage. Extrahepatic features sometimes observed in PFIC1 include sensorineural hearing loss, diarrhea, pancreatitis, and short stature. ATP8B1 was shown to translocate phospholipids across the plasma membrane; however, expression of ATP8B1 in many tissues and the range of pathological manifestations in ATP8B1 deficiency suggest diverse physiological functions of ATP8B1, and pleiotropic mechanisms regulating its activity. Recent studies suggest that phosphoinositides, including PIP2 and PIP3, can function as regulators, substrates, and binding partners of ATP8B1. New research shows that ATP8B1 modulates host immune system by regulating cleavage of pyroptotic-executioner Gasdermin D (GSDMD), and inflammation-resolution pathways such as phagocytosis/efferocytosis. Further mechanistic insights can accelerate development of new therapies for restoring membrane integrity, reducing inflammasome activity, and correcting metabolic imbalances caused by ATP8B1 dysfunction.

Stem cells play a critical role in tissue regeneration and the maintenance of homeostasis. Due to their high replicative potential, stem cells face an elevated risk of DNA damage during DNA replication. Consequently, efficient DNA damage repair (DDR) mechanisms are essential for preserving the genomic stability and functionality of stem cells. This review summarizes the main DNA damage repair mechanisms, examines the characteristics of these DDR pathways in different stem cell types (highlighting their specific features and key molecules), and discusses the clinical significance and applications of stem cell DDR research. Furthermore, we identify current research limitations and propose potential future research directions. Collectively, this review provides a comprehensive perspective on DDR mechanisms in stem cells, laying a foundation for future investigations and potential clinical applications.

Heat shock protein 22 (HSP22) can reduce type 2 diabetes mellitus (T2DM) induced vascular endothelial injury by inhibition of inflammation and oxidative stress. Therefore, we explored whether HSP22 alleviated diabetes cardiomyopathy (DCM) in mice. A T2DM mouse model was constructed and myocardial tissues were used to perform transcriptome sequencing. HSP22 transgenic and HSP22 knockout mice were established to confirm its role in DCM. Transthoracic echocardiography, hematoxylin-eosin staining, TUNEL staining and apoptosis-related proteins were detected to evaluate myocardial injury. Dihydroethidium staining, malondialdehyde and superoxide dismutase levels were detected to evaluate myocardial oxidative stress. We performed RT-PCR to detect inflammatory factors and evaluate the myocardial inflammatory response. Immunohistochemical staining, RT-PCR and western blot were used to define the expression of HSP22 in mouse myocardial tissues. Transcriptome sequencing analysis revealed the expression of HSP22 in myocardium of T2DM mice significantly decreases. GO analysis found that oxidative stress and inflammatory response were closely related to DCM in mice. Furthermore, HSP22 overexpression can alleviate DCM in mice and HSP22 knockout aggravated DCM. HSP22 reduced oxidative stress and inflammation to alleviate DCM in mice.

Breast cancer (BC) is identified as a significant cause of cancer mortality in the female population. The recurrence of initial tumors and the metastasis to remote areas of the body are significant factors leading to the mortality linked with BC. Despite the advancements in diagnostic and therapeutic approaches, a comprehensive understanding of the molecular mechanisms underlying metastasis is still unclear, particularly regarding the regulatory role of non-coding RNAs (ncRNAs) in epithelial-mesenchymal transition (EMT). Different categories of ncRNAs, including microRNAs (miRNAs), circular RNAs (circRNAs), and long ncRNAs (lncRNAs), can manage the complex regulatory frameworks of EMT at various levels. Since dysregulation of ncRNAs is associated with key processes in EMT, investigating them as valuable tools for identifying the metastatic potential of tumors at an early stage could significantly increase diagnostic accuracy and improve patient outcomes, particularly in BC. This review aims to bridge this gap by systematically summarizing current insights into the interplay between EMT and various classes of ncRNAs in the context of BC progression. We discuss the molecular pathways through which ncRNAs regulate EMT, their impact on metastasis and explore their potential as diagnostic biomarkers and therapeutic targets. By providing an integrative overview of recent findings, this article highlights unresolved questions and proposes directions for future research, offering a valuable resource for researchers and clinicians involved in breast cancer biology and treatment development.

Hepatocellular carcinoma (HCC) is a highly aggressive liver cancer, and its progression is significantly influenced by the tumor microenvironment (TME). Tumor-derived exosomes (TEXs), an important component of the TME, significantly influence tumor growth by regulating immune responses, facilitating metastasis, and enhancing resistance to therapy. These extracellular vesicles (EVs) transport bioactive substances, such as proteins, lipids, and nucleic acids that promote interaction between cells in the TME. Recent research indicates that HCC-derived exosomes can inhibit immune cell activity, specifically in T cells, thus creating an immunosuppressive TME that facilitates tumor immune escape. They also augment metastatic capability by restructuring the extracellular matrix and promoting angiogenesis. Moreover, HCC-derived exosomes have been associated with developing resistance to drug therapy by transferring molecules such as apoptotic signals and oncogenic microRNAs, circRNAs and lncRNA. Understanding how HCC-derived exosomes affect immune modulation, metastasis, and drug resistance could yield innovative therapeutic targets to enhance therapy outcomes. This review focuses on recent research on the diverse functions of TEXs in HCC progression.

Ranking second out of new cancer cases, breast cancer (BRCA) is the leading cause of cancerous death among women globally. Methyltransferase-like 3 (METTL3), as the well-known N6‑methyladenosine (m6A) "writer" with catalytic function, regulates cancer progression through specific downstream targets, but its interplay with epidermal growth factor (EGF) signaling in BRCA is poorly defined. Here, we depict a METTL3-m6A-EGF axis in BRCA, where BRCA cell properties were affected by METTL3 through m6A-dependent expression of EGF. We observed the correlation between METTL3 expression in BRCA tissues and negative prognosis through bioinformatics analysis and RT-qPCR. In vitro lentiviral-mediated METTL3 knockdown suppressed proliferation and migration, while the in vivo tumor formation experiment in nude mice validated the tumor-promoting effect of METTL3. Hematoxylin-eosin staining and immunohistochemistry also showed the tumor-promoting effect of METTL3. Mechanistically, METTL3 stabilized EGF mRNA via m6A modification, as evidenced by MeRIP-qPCR and Western blotting. Notably, METTL3 maintains EGF/EGFR signaling, and its overexpression leads to insensitivity to gefitinib and adriamycin. We naturally conclude that METTL3 is a central epigenetic regulator of EGF-driven BRCA progression, providing a rationale for targeting METTL3 to overcome chemotherapeutic resistance.