Ferroptosis hallmarked by lipid peroxidation and iron homeostasis imbalance is involved in the occurrence and development of various diseases. The plant growth regulator chlormequat chloride (CCC) can contribute to the causality and exacerbation of reproductive disorders. However, the mechanism by which CCC may cause Leydig cell attenuation remains poorly understood. In this study, TM3 Leydig cells were used to investigate the inhibitory effect of CCC on cell growth and its possible mechanism. The results showed that CCC caused apoptosis, pyroptosis, ferroptosis and necroinflammation in TM3 cells. By comparing the effects of ferroptosis inhibitor Ferrostatin-1 (Fer-1) and pan-Caspase inhibitor Z-VAD-FMK (ZVF) on lipid peroxidation and Caspase-mediated regulated cell death (RCD), we found that Fer-1 was better at rescuing the growth of TM3 cells than ZVF. Although ZVF reduced mitochondrial ROS level and inhibited the activation of Caspase3 and Caspase1, it could not significantly ameliorate lipid peroxidation and the levels of IL-1β and HMGB1 like Fer-1. Therefore, ferroptosis might be a key non apoptotic RCD mode responsible for CCC-driven inflammation, leading to weakened viability and proliferation of TM3 cells. In addition, overexpression of ferritin light chain (FTL) promoted the resistance of TM3 cells to CCC-induced ferroptosis-mediated inflammation and to some extent improved the inhibition of viability and proliferation. Altogether, ferroptosis-initiated inflammation might play a key role in CCC-impaired TM3 cell growth.

Breast cancer arises from the malignant transformation of mammary epithelial cells under the influence of various carcinogenic factors, leading to a gradual increase in its prevalence. This disease has become the leading cause of mortality among female malignancies, posing a significant threat to the health of women. The timely identification of breast cancer remains challenging, often resulting in diagnosis at the advanced stages of the disease. Conventional therapeutic approaches, such as surgical excision, chemotherapy and radiotherapy, exhibit limited efficacy in controlling the progression and metastasis of the disease. Regulated cell death (RCD), a process essential for physiological tissue cell renewal, occurs within the body independently of external influences. In the context of cancer, research on RCD primarily focuses on cuproptosis, ferroptosis and pyroptosis. Mounting evidence suggests a marked association between these specific forms of RCD, and the onset and progression of breast cancer. For example, a cuproptosis vector can effectively bind copper ions to induce cuproptosis in breast cancer cells, thereby hindering their proliferation. Additionally, the expression of ferroptosis‑related genes can enhance the sensitivity of breast cancer cells to chemotherapy. Likewise, pyroptosis‑related proteins not only participate in pyroptosis, but also regulate the tumor microenvironment, ultimately leading to the death of breast cancer cells. The present review discusses the unique regulatory mechanisms of cuproptosis, ferroptosis and pyroptosis in breast cancer, and the mechanisms through which they are affected by conventional cancer drugs. Furthermore, it provides a comprehensive overview of the significance of these forms of RCD in modulating the efficacy of chemotherapy and highlights their shared characteristics. This knowledge may provide novel avenues for both clinical interventions and fundamental research in the context of breast cancer.

Cell death plays a crucial part in the process of age-related macular degeneration (AMD), but its mechanisms remain elusive. Accumulating evidence suggests that ferroptosis, a novel form of regulatory cell death characterized by iron-dependent accumulation of lipid hydroperoxides, has a crucial role in the pathogenesis of AMD. Numerous studies have suggested that ferroptosis participates in the degradation of retinal cells and accelerates the progression of AMD. Furthermore, inhibitors of ferroptosis exhibit notable protective effects in AMD, underscoring the significance of ferroptosis as a pivotal mechanism in the death of retinal cells during the process of AMD. This review aims to summarize the molecular mechanisms of ferroptosis in AMD, enumerate potential inhibitors and discuss the challenges and future opportunities associated with targeting ferroptosis as a therapeutic strategy, providing important information references and insights for the prevention and treatment of AMD.

Programmed cell death (PCD), also known as regulatory cell death (RCD), is a process that occurs in all organisms and is closely linked to both normal physiological processes and disease states. Various signaling pathways, such as TP53, KRAS, NOTCH, hypoxia, and metabolic reprogramming, have been found to regulate RCD. Polysaccharides, which are essential natural products, have been the subject of extensive research in the fields of food, nutrition, and medicine due to their wide range of pharmacological effects. Studies have shown that polysaccharides have biological activities and the potential to target signal transduction pathways for the treatment of diseases. This paper provides a review of the mechanisms through which polysaccharides exert their therapeutic effects at different levels and explores the relationship between different types of RCD and human diseases. The aim of this review is to provide a theoretical basis for the further clinical use and application of polysaccharide bioactivities.

Copper (Cu) plays a crucial and diverse function in biological systems, acting as a cofactor at numerous sites of enzymatic activity and participating in various physiological processes, including oxidative stress regulation, lipid metabolism, and energy metabolism. Similar to other micronutrients, the body regulates Cu levels to ensure homeostasis; any disruption in Cu homeostasis may result in various illnesses. Cuproptosis causes proteotoxic stress and ultimately results in cell death by the binding of Cu ions to lipid-acylated proteins during the tricarboxylic acid cycle of mitochondrial respiration. Cu is not only involved in regulatory cell death (RCD), but also in exogenous factors that induce cellular responses and toxic outcomes. Cu imbalances also affect the transmission of several RCD messages. Therefore, this article presents a thorough examination of the mechanisms involved in Cu-induced RCD as well as the role of Cu complexes in its pathophysiology.

Diabetes mellitus is a metabolic disease that is characterized by chronic hyperglycemia due to a variety of etiological factors. Long-term metabolic stress induces harmful inflammation leading to chronic complications, mainly diabetic ophthalmopathy, diabetic cardiovascular complications and diabetic nephropathy. With diabetes complications being one of the leading causes of disability and death, the use of anti-inflammatories in combination therapy for diabetes is increasing. There has been increasing interest in targeting significant regulators of the inflammatory pathway, notably receptor-interacting serine/threonine-kinase-1 (RIPK1) and receptor-interacting serine/threonine-kinase-3 (RIPK3), as drug targets for managing inflammation in treating diabetes complications. In this review, we aim to provide an up-to-date summary of current research on the mechanism of action and drug development of RIPK1 and RIPK3, which are pivotal in chronic inflammation and immunity, in relation to diabetic complications which may be benefit for explicating the potential of selective RIPK1 and RIPK3 inhibitors as anti-inflammatory therapeutic agents for diabetic complications.

Cardiovascular disease (CVD) is currently one of the prevalent causes of human death. Iron is one of the essential trace elements in the human body and a vital component of living tissues. All organ systems require iron for various metabolic processes, including myocardial and skeletal muscle metabolism, erythropoiesis, mitochondrial function, and oxygen transport. Its deficiency or excess in the human body remains one of the nutritional problems worldwide. The total amount of iron in a normal human body is about 3-5 g. Iron deficiency may cause symptoms such as general fatigue, pica, and nerve deafness, while excessive iron plays a crucial role in the pathophysiological processes of the heart through ferroptosis triggered by the Fenton reaction. It differs from other cell death modes based on its dependence on the accumulation of lipid peroxides and REDOX imbalance, opening a new pathway underlying the pathogenesis and mechanism of CVDs. In this review, we describe the latest research progress on the mechanism of ferroptosis and report its crucial role and association with miRNA in various CVDs. Finally, we summarise the potential therapeutic value of ferroptosis-related drugs or ferroptosis inhibitors in CVDs.

Copper, a transition metal, serves as an essential co-factor in numerous enzymatic active sites and constitutes a vital trace element in the human body, participating in crucial life-sustaining activities such as energy metabolism, antioxidation, coagulation, neurotransmitter synthesis, iron metabolism, and tetramer deposition. Maintaining the equilibrium of copper ions within biological systems is of paramount importance in the prevention of atherosclerosis and associated cardiovascular diseases. Copper induces cellular demise through diverse mechanisms, encompassing reactive oxygen species responses, apoptosis, necrosis, pyroptosis, and mitochondrial dysfunction. Recent research has identified and dubbed a novel regulatory cell death modality-\"cuprotosis\"-wherein copper ions bind to acylated proteins in the tricarboxylic acid cycle of mitochondrial respiration, resulting in protein aggregation, subsequent downregulation of iron-sulfur cluster protein expression, induction of proteotoxic stress, and eventual cell death. Scholars have synthesized copper complexes by combining copper ions with various ligands, exploring their significance and applications in cancer therapy. This review comprehensively examines the multiple pathways of copper metabolism, copper-induced regulatory cell death, and the current status of copper complexes in cancer treatment.

Diabetic nephropathy (DN) and diabetic retinopathy (DR) are the most serious and common diabetes-associated complications. DN and DR are all highly prevalent and dangerous global diseases, but the underlying mechanism remains to be elucidated. Ferroptosis, a relatively recently described type of cell death, has been confirmed to be involved in the occurrence and development of various diabetic complications. The disturbance of cellular iron metabolism directly triggers ferroptosis, and abnormal iron metabolism is closely related to diabetes. However, the molecular mechanism underlying the role of ferroptosis in DN and DR is still unclear, and needs further study. In this review article, we summarize and evaluate the mechanism of ferroptosis and its role and progress in DN and DR, it provides new ideas for the diagnosis and treatment of DN and DR.

Diabetes is a common chronic metabolic disease, and its incidence continues to increase year after year. Diabetic patients mainly die from various complications, with the most common being diabetic cardiomyopathy. However, the detection rate of diabetic cardiomyopathy is low in clinical practice, and targeted treatment is lacking. Recently, a large number of studies have confirmed that myocardial cell death in diabetic cardiomyopathy involves pyroptosis, apoptosis, necrosis, ferroptosis, necroptosis, cuproptosis, cellular burial, and other processes. Most importantly, numerous animal studies have shown that the onset and progression of diabetic cardiomyopathy can be mitigated by inhibiting these regulatory cell death processes, such as by utilizing inhibitors, chelators, or genetic manipulation. Therefore, we review the role of ferroptosis, necroptosis, and cuproptosis, three novel forms of cell death in diabetic cardiomyopathy, searching for possible targets, and analyzing the corresponding therapeutic approaches to these targets.