Apoptosis最新文献

Recent studies have suggested that sVEGFR3 is involved in cardiac diseases by regulating lymphangiogenesis; however, results are inconsistent. The aim of this study was to investigate the function and mechanism of sVEGFR3 in myocardial ischemia/reperfusion injury (MI/RI). sVEGFR3 effects were evaluated in vivo in mice subjected to MI/RI, and in vitro using HL-1 cells exposed to oxygen-glucose deprivation/reperfusion. Echocardiography, TTC-Evans blue staining, ELISA, electron microscopy, immunofluorescence, western blotting, and flow cytometry were used to investigate whether sVEGFR3 attenuates I/R injury. Transcriptome sequencing was used to investigate the downstream mechanism of sVEGFR3. Results showed that, in vivo, sVEGFR3 pretreatment reduced cardiac dysfunction, infarct area, and myocardial injury indicators by reducing ROS production, AIF expression, and apoptosis. In vitro, sVEGFR3 restored mitochondrial homeostasis by stabilizing the mitochondrial membrane potential (MMP) and preventing the opening of mitochondrial permeability transition pores (mPTP). And sVEGFR3 inhibits mitochondrial apoptosis through the Ras/MEK/ERK pathway. Furthermore, I/R injury increased the proportion of M1 macrophages and CD4 + T cells in myocardial tissue, as well as serum IFN-γ and TNF-α levels, whereas sVEGFR3 treatment attenuated these effects. sVEGFR3 attenuates MI/RI by regulating mitochondrial homeostasis and immune cell infiltration, and reduces intrinsic ROS-mediated mitochondrial apoptosis via the Ras/MEK/ERK pathway.

Ovarian cancer remains a major challenge in oncology due to its complex biology and late-stage diagnosis. Recent advances in molecular biology have highlighted the crucial role of non-coding RNAs (ncRNAs) in regulating apoptosis and cancer progression. NcRNAs, including microRNAs, long non-coding RNAs, and circular RNAs, have emerged as significant players in the molecular networks governing ovarian cancer. Despite these insights, the precise mechanisms by which ncRNAs influence ovarian cancer pathology are not fully understood. This complexity, combined with the heterogeneity of the disease and the development of treatment resistance, poses substantial obstacles to effective therapeutic development. Additionally, the lack of reliable early detection methods further complicates treatment strategies. This manuscript reviews the current state of research on ncRNAs in ovarian cancer, discusses the challenges in translating these findings into clinical applications, and outlines potential future directions. Emphasis is placed on the need for integrated approaches to unravel the intricate roles of ncRNAs, improve early detection, and develop personalized treatment strategies to address the diverse and evolving nature of ovarian cancer. While these findings provide valuable insights, it is crucial to recognize that many results are based on preclinical studies and require further validation to establish their clinical applicability.

This study investigates silibinin's capacity to mitigate Alzheimer's disease (AD) pathologies with a particular emphasis on its effects on apoptosis and synaptic dysfunction in AD models. Employing APP/PS1 transgenic mice and SH-SY5Y neuroblastoma cell lines, our research assessed the efficacy of silibinin in reducing amyloid-beta (Aβ) deposition, neuroinflammation, and neuronal apoptosis. Our results demonstrate that silibinin significantly decreases Aβ accumulation and neuroinflammation and robustly inhibits apoptosis in neuronal cells. Additionally, silibinin enhances the expression of synaptic proteins, thereby supporting synaptic integrity. Through network pharmacology analysis, we identified potential targets of silibinin in Aβ metabolism and synaptic functions. Mechanistically, our findings suggest that silibinin promotes neuronal survival predominantly via the modulation of the Fyn/GluN2B/CaMKIIα signaling pathway, which protects against Aβ1-42-induced apoptosis. These insights highlight silibinin's potential as a therapeutic agent for AD, particularly its role in reducing neuronal apoptosis and maintaining synaptic function.

Kidney diseases represent a significant global public health challenge, characterized by complex pathogenesis, high incidence, low awareness, insufficient early screening, and substantial treatment disparities. Effective therapeutic options remain lacking. Programmed cell death (PCD), including apoptosis, pyroptosis, and necroptosis, play pivotal roles in the pathogenesis of various kidney diseases. In 2019, PANoptosis, a novel form of inflammatory cell death, was introduced, providing new insights into innate immunity and PCD research. Although research on PANoptosis in kidney diseases is still limited, identifying key molecules within PANoptosomes and understanding their regulatory roles is critical for disease prevention and management. This review summarizes the various forms of PCD implicated in kidney diseases, along with PANoptosomes activated by Z-DNA binding protein 1 (ZBP1), absent in melanoma 2 (AIM2), receptor-interacting protein kinase 1 (RIPK1), NOD-like receptor family CARD domain containing 12 (NLRP12), and NOD-like receptor family member C5 (NLRC5). It also reviews the advancements in PANoptosis research in the field of kidney diseases, particularly in renal tumors and acute kidney injuries (AKI). The goal is to establish a foundation for future research into the role of PANoptosis in kidney diseases.

Obesity and related metabolic disorders are closely linked to increased apoptosis in skeletal muscle, leading to muscle degeneration, insulin resistance, and the progression of diseases such as type 2 diabetes and sarcopenia. This review explores the combined effects of natural products, including resveratrol, curcumin, and quercetin, and physical exercise on modulating apoptosis pathways in skeletal muscle. Both natural products and regular physical activity independently reduce oxidative stress and improve mitochondrial function, thereby regulating the balance between pro-apoptotic and anti-apoptotic signals. When combined, these interventions amplify their protective effects on muscle health, promoting mitochondrial biogenesis, reducing apoptosis, and enhancing muscle regeneration. This review also discusses the molecular mechanisms by which these strategies influence apoptosis, with a focus on the Bcl-2 pathway, and explores the clinical implications for the prevention and treatment of obesity-related diseases. The synergistic benefits of combining exercise with natural product supplementation offer a promising therapeutic approach for managing metabolic disorders, preserving muscle function, and improving overall metabolic health.

Cardiovascular disease (CVD) is a leading cause of human mortality worldwide, with patients often at high risk of heart failure (HF) in myocardial infarction (MI), a common form of CVD that results in cardiomyocyte death and myocardial necrosis due to inadequate myocardial perfusion. As terminally differentiated cells, cardiomyocytes possess a severely limited capacity for regeneration, and an excess of dead cardiomyocytes will further stress surviving cells, potentially exacerbating to more extensive heart disease. The article focuses on the relationship between programmed cell death (PCD) of cardiomyocytes, including different forms of apoptosis, necrosis, and autophagy, and MI, as well as the potential application of these mechanisms in the treatment of MI. By gaining a deeper understanding of the mechanisms of cardiomyocyte death, it aims to provide new insights into the prevention and treatment of MI.

Despite advances in treatment, the prognosis of osteosarcoma (OS) patients is unsatisfactory, and searching for possible targets is substantial. Fibroblast growth factor inducible type 14 (FN14), a plasma membrane protein, is involved in wound healing, angiogenesis, proliferation, apoptosis, and inflammation. However, its implication in OS development and progression has not been completely characterized. Herein, we explored the cell-to-cell communication of bone marrow mesenchymal stem cells (BMSCs) and OS cells mediated by FN14 in the tumor microenvironment of OS. To assess the interplay between FN14 expression levels and patient survival, FN14 expression was measured in both normal and OS tissues. The FN14 overexpressing BMSCs (OE) were constructed using lentivirus, and exosomes (EXO) were extracted. The uptake of FN14-containing EXO by OS cells was analyzed via flow cytometry and in vivo fluorescence imaging. In addition, high-throughput sequencing was performed to analyze the mechanisms by which EXO inhibits OS cell growth. Finally, the therapeutic effect of OE-EXO was evaluated in a mouse model of OS xenografts. The results showcased reduced FN14 expression in human and mouse OS tissues, suggesting its role may be involved in the malignant progression of OS. The FN14 expression was higher in BMSCs relative to OS cells, and FN14 was secreted and excreted by EXO. The OS cell progression was suppressed after the uptake of FN14-derived EXO from BMSCs. In addition, RNA sequencing revealed that FN14 in EXO activated NF-κB signaling, triggering PANoptosis in OS cells. In vivo, OE-EXO injection inhibited tumor growth in OS xenografts and significantly improved the long-term survival of mice. Our findings suggest that FN14 carried by EXO from BMSCs activates the NF-κB pathway to trigger PANoptosis in OS cells, providing a potential therapeutic strategy to inhibit OS progression.

Necroptosis is a finely regulated programmed cell death process involving complex molecular mechanisms and signal transduction networks. Among them, receptor-interacting protein kinase 1 (RIPK1), receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like protein are the key molecules regulating this process. In recent years, gasotransmitters such as nitric oxide, carbon monoxide and hydrogen sulfide have been suggested to play a regulatory role in necroptosis. This paper reviews the evidence that these gasotransmitters are involved in the regulation of necroptosis by influencing the production of reactive oxygen species, regulating the modification of S subunits of RIPK1 and RIPK3, regulating inflammatory mediators, and signal transduction. In addition, this review explores the potential therapeutic applications of these gasotransmitters in pathological conditions such as cardiovascular disease and ischemia-reperfusion injury. Although some studies have revealed the important role of gasotransmitters in necroptosis, the specific mechanism of action is still not fully understood. Future research is needed to further elucidate the molecular mechanisms of gasotransmitters in precisely regulating necroptosis, which will help develop new therapeutic strategies to prevent and treat related diseases.

Cancer-associated fibroblasts (CAFs) significantly influence tumor progression and therapeutic resistance in colorectal cancer (CRC). However, the distributions and functions of CAF subpopulations vary across the four consensus molecular subtypes (CMSs) of CRC. This study performed single-cell RNA and bulk RNA sequencing and revealed that myofibroblast-like CAFs (myCAFs), tumor-like CAFs (tCAFs), inflammatory CAFs (iCAFs), CXCL14⁺CAFs, and MT⁺CAFs are notably enriched in CMS4 compared with other CMSs of CRC. Multiplex immunohistochemistry was used to validate the distribution of CAF subtypes in patients with different CMSs. Prognosis-related CAF subtypes were identified, leading to the selection of four key genes (COL3A1, COL1A2, GEM, and TMEM47). Through machine learning, we developed a CAF poor-prognosis gene (CAFPRG) model to predict outcomes of patients with CMS4. High levels of CAFPRGs were identified as independent poor-risk factors for prognosis (p < 0.001). Tumors with elevated CAFPRGs exhibited increased infiltration of immune-suppressive cells and resistance to chemotherapy. The expression of these key genes was confirmed to be significantly higher in CAFs than in normal fibroblasts (NFs). Therefore, CAFPRGs may be valuable for precisely predicting patient survival and may present potential therapeutic opportunities for CMS4 CRC.