Apoptosis最新文献

Diabetes mellitus is a common chronic metabolic disease, with its prevalence escalating annually. Diabetic cardiomyopathy is a leading cause of mortality among diabetic patients, characterized by intricate metabolic disturbances and myocardial cell demise. Various forms of cellular death pathways including apoptosis, pyroptosis, autophagic cell death, necroptosis, ferroptosis, and entosis have been identified in diabetic cardiomyopathy. Inhibiting myocardial cell death pathways has shown promise in mitigating diabetic cardiomyopathy progression. However, there are still gaps in understanding the role of metal ions in diabetic cardiomyopathy pathogenesis. Recent research endeavors have found that iron, copper, zinc, calcium, manganese and other metal elements related to cell death play an intricate and critical role in the pathogenesis and progression of diabetic cardiomyopathy. Notably, many animal studies have shown that the development and progression of diabetic cardiomyopathy can be alleviated by inhibiting the cell death process induced by these metal ions. Therefore, we review the molecular mechanisms underlying the death of various metal ions and the potential pathophysiological roles they play in diabetic cardiomyopathy. In addition, the value of these metal ions in the treatment of diabetic cardiomyopathy is also described.

Postoperative cognitive dysfunction (POCD) is a prevalent complication affecting the central nervous system after surgery, manifesting as a decline in cognitive abilities, particularly common among elderly patients. Surgical stress and anesthesia can activate systemic inflammation, prompting immune cells, including neutrophils, to infiltrate the brain, thereby triggering neuroinflammation and resulting in cognitive impairment. Neutrophils, as crucial effector cells in innate immunity, have been increasingly recognized in recent years for their significant role in the pathogenesis of POCD due to their vital function in inflammatory responses. They are not only rapidly activated in peripheral blood, secreting a range of cytokines, chemokines, and neutrophil extracellular traps (NETs), but also possess the capacity to alter the permeability of the blood-brain barrier (BBB), further facilitating the development of neuroinflammation. This paper systematically reviews the recent findings on the diverse functions of neutrophils and their role in POCD, aiming to provide novel theoretical foundations and cutting-edge perspectives for advancing foundational research and optimizing clinical intervention strategies for POCD.

Autophagy is a vital pathway for recycling and degrading intracellular materials, closely linked to tumorigenesis and progression. The ubiquitin-specific protease (USP) family, as a critical group of deubiquitinating enzymes, plays a complex part in regulating autophagy, metabolism, immune responses, and tumor cells' resistance to drugs. By modifying autophagy-associated proteins through deubiquitination, the USP family influences tumor cell proliferation, survival, and metabolism. Additionally, these enzymes are involved in modulating immune responses within the tumor microenvironment, thereby impacting tumor immune escape. Regarding drug resistance, the USP family enhances the tolerance of tumor cells to chemotherapeutic agents by promoting autophagy. Therefore, targeting USP family members and their regulated autophagy processes may offer new avenues for cancer therapy. This review examines the function of the USP family in tumor autophagy regulation and its implications for tumor progression. The goal of future studies should be to clarify the molecular mechanisms underlying USP-autophagy interactions and their specific roles in various tumor types to establish a theoretical framework for developing novel cancer therapeutic strategies.

Premature ovarian insufficiency (POI) is a multifactorial condition characterized by diminished ovarian function, granulosa cell (GC) apoptosis, and impaired ovarian angiogenesis, leading to infertility and long-term health complications. Despite its prevalence, effective therapeutic targets for POI remain limited. This study investigates the role of CCDC134 in maintaining ovarian reserve and promoting angiogenesis and its interaction with INHA in a mouse model of POI. Ovarian granulosa cells from POI patients and unaffected women were analyzed for apoptosis and CCDC134 expression. A cisplatin-induced mouse model of POI was used to evaluate the therapeutic potential of AAV-mediated ovary-specific overexpression of CCDC134. Ovarian morphology, hormonal levels, follicular development, granulosa cell viability, and angiogenesis were assessed. The interaction between CCDC134 and INHA was examined using co-immunoprecipitation, immunofluorescence, and molecular pathway analyses. CCDC134 expression was significantly downregulated in ovarian tissues and granulosa cells of POI patients and cisplatin-induced POI mice. CCDC134 overexpression improved ovarian morphology, restored follicular development across all stages, and enhanced reproductive outcomes in POI mice. Hormonal imbalances, including decreased AMH and E2 and elevated FSH and LH, were reversed following CCDC134 overexpression. Moreover, CCDC134 treatment significantly reduced GC apoptosis by downregulating pro-apoptotic markers (Caspase-3 and Bax) and upregulating anti-apoptotic Bcl-2. Angiogenesis was enhanced, as indicated by increased expression of CD34 and vWF, improved endothelial cell viability, and restored VEGF levels. Mechanistic studies revealed a direct interaction between CCDC134 and INHA, with CCDC134 promoting INHA expression and modulating apoptotic and angiogenic pathways. CCDC134 plays a critical role in maintaining ovarian reserve and promoting angiogenesis by directly interacting with INHA. Its overexpression restores ovarian function, mitigates granulosa cell apoptosis, and enhances angiogenesis in a mouse model of POI. These findings highlight the therapeutic potential of the CCDC134-INHA axis as a novel strategy for treating POI.

Pulmonary arterial hypertension (PAH) is a heterogeneous disease characterized by various etiologies, with pulmonary vascular remodeling recognized as a main pathological change. Currently, it is widely accepted that vascular remodeling is closely associated with abnormal pulmonary vascular cell death and perivascular inflammation. The simultaneous activation of various pulmonary vascular cell death leads to immune cell adhesion and inflammatory mediator releases; And in turn, the inflammatory response may also trigger cell death and jointly promote the progression of vascular remodeling. Recently, PANoptosis has been identified as a phenomenon that describes the simultaneous activation and interaction of multiple forms of programmed cell death (PCD). Therefore, the relationship between PANoptosis and inflammation in PAH warrants further investigation. This review examines the mechanisms underlying apoptosis, necroptosis, pyroptosis, and inflammatory responses in PAH, with a focus on PANoptosis and its interactions with inflammation. And it aims to elucidate the significance of this emerging form of cell death and inflammation in the pathophysiology of PAH and to explore its potential as a therapeutic target.