Artemisinin (ART) is a bioactive molecule derived from the Chinese medicinal plant Artemisia annua (Asteraceae). ART and artemisinin derivatives (ARTs) have been effectively used for antimalaria treatment. The structure of ART is composed of a sesquiterpene lactone, including a peroxide internal bridge that is essential for its activity. In addition to their well‐known antimalarial effects, ARTs have been shown recently to resist a wide range of tumors. The antineoplastic mechanisms of ART mainly include cell cycle inhibition, inhibition of tumor angiogenesis, DNA damage, and ferroptosis. In particular, ferroptosis is a novel nonapoptotic type of programmed cell death. However, the antitumor mechanisms of ARTs by regulating ferroptosis remain unclear. Through this review, we focus on the potential antitumor function of ARTs by acting on ferroptosis, including the regulation of iron metabolism, generation of reactive oxygen species (ROS), and activation of endoplasmic reticulum stress (ERS). This article systematically reviews the recent progress in ferroptosis research and provides a basis for ARTs as an anticancer drug in clinical practice.

The irreversible degeneration of dopamine neurons induced by α-synuclein (α-syn) aggregation in the substantia nigra is the central pathological feature of Parkinson's disease (PD). Neuroimaging and pathological autopsy studies consistently confirm significant iron accumulation in the brain of PD patients, suggesting a critical role for iron in disease progression. Current research has established that iron overload induces ferroptosis in dopaminergic neurons, evidence indicates that the impact of iron on PD pathology extends beyond ferroptosis. Iron also plays a regulatory role in modulating α-syn, affecting its aggregation, spatial conformation, post-translational modifications, and mRNA stability. Iron-induced α-syn aggregation can contribute to dopaminergic neurodegeneration through additional mechanisms, potentially creating a feedback loop in which α-syn further enhances iron accumulation, thus perpetuating a vicious cycle of neurotoxicity. Given α-syn’s intrinsically disordered structure, targeting iron metabolism presents a promising therapeutic strategy for PD. Therefore, the development of iron chelators, alone or in combination with other therapeutic drugs, may offer a beneficial approach to alleviating PD symptoms and slowing disease progression.

Parkinson’s disease (PD) is a neurodegenerative disease second only to Alzheimer’s disease in terms of prevalence. Previous studies have indicated that the occurrence and progression of PD are associated with mitochondrial dysfunction. Mitochondrial dysfunction is one of the most important causes for apoptosis of dopaminergic neurons. Therefore, maintaining the stability of mitochondrial functioning is a potential strategy in the treatment of PD. Voltage‐dependent anion channel (VDAC) is the main component in the outer mitochondrial membrane, and it participates in a variety of biological processes. In this review, we focus on the potential roles of VDACs in the treatment of PD. We found that VDACs are involved in PD by regulating apoptosis, autophagy, and ferroptosis. VDAC1 oligomerization, VDACs ubiquitination, regulation of mitochondrial permeability transition pore (mPTP) by VDACs, and interaction between VDACs and α‐synuclein (α‐syn) are all promising methods for the treatment of PD. We proposed that inhibition of VDAC1 oligomerization and promotion of VDAC1 ubiquitination as an effective approach for the treatment of PD. Previous studies have proven that the expression of VDAC1 has a significant change in PD models. The expression levels of VDAC1 are decreased in the substantia nigra (SN) of patients suffering from PD compared with the control group consisting of normal individuals by using bioinformatics tools. VDAC2 is involved in PD mainly through the regulation of apoptosis. VDAC3 may have a similar function to VDAC1. It can be concluded that the functional roles of VDACs contribute to the therapeutic strategy of PD.

Background: Breast cancer (BC) has become the main malignant tumor threatening the health of women worldwide. Previous studies have reported that Lactate dehydrogenase-A (LDHA) has critical roles in cancer development and progression. We aimed to explore the roles of LDHA and LDH5 isoenzyme activity in BC, which provides a new insight into LDHA for the treatment of BC. Methods: The expression of LDHA in BC and its relationship with clinicopathological features were obtained from various databases including The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA), Breast Cancer-Gene Expression Miner (bc-GenExMiner), TNMplot, UALCAN. The Kaplan‒Meier Plotter was used to evaluate the prognostic value of LDHA. Western blot was performed to detect LDHA expression. Agarose gel electrophoresis was performed to detect the activities of LDH isoenzymes. The in vitro proliferation, migration and invasion potentials of BC cells were evaluated using MTT assays, colony formation, wound-healing assay, matrix metalloproteinase assays and transwell assays, respectively. The activities of LDH isoenzymes in serum and tissues were measured in patients with BC and healthy controls. Results: Compared to normal tissues, LDHA expression was significantly higher in BC tissues. Patients’ nodal status, histological types, TP53 mutation status and PAM50 subtypes were significant factors influencing the LDHA expression. By overexpressing or silencing LDHA gene in BT549 cells, it was confirmed that LDHA promoted cell proliferation, migration and invasion. LDH5 isoenzyme activity in patients with BC was higher than healthy controls. The increased activity of LDH5 isoenzymes was induced by overexpression of LDHA in BC. High expression of LDHA was found to be associated with poor prognosis in BC. Conclusion: LDHA plays a critical role in the progression of BC through the regulation of the activity of LDH5 isoenzyme, indicating that LDHA may serve as a valuable target for BC treatment.

Research has demonstrated that hypoxia, a decrease in intracellular oxygen, is linked to multiple processes in the skin, including metabolic adaptation, cell survival, pathogenic microbe infection, immune response, tumorigenesis, and various diseases. This paper aims to perform a thorough bibliometric analysis of studies of hypoxia in skin health and disease to identify the frontiers, hotspots, and evolution of these studies. Articles about hypoxia in skin health and disease in the Web of Science Core Collection were gathered as of 31 December 2023. To find bursting keywords and references, VOSviewer was used to look at co-authorship and phrase co-occurrences and make visualizations of them. A total of 1,511 papers on hypoxia in skin health and disease were examined in this study. China, the United States, and Japan were the top three countries contributing to this topic, while the International Journal of Molecular Sciences was the journal with the most articles. In terms of prolific authors in the publications, Yuesheng Huang from China contributed the most articles. The terms “hypoxia,” “angiogenesis,” and “wound healing” were the ones that were used the most frequently. In this study, a bibliometric analysis was performed on the last ten years’ worth of research on hypoxia in skin health and disease. The analysis identified the publications, nations, authors, institutions, and journals that were involved in this subject. These data offer a more comprehensive understanding of the area of research that has been conducted on hypoxia in skin health and disease.

Background: Postsurgical distant metastasis remains the leading cause of breast cancer-related mortality, yet reliable biomarkers for identifying patients at high risk of recurrence are lacking. Tumor necrosis factor alpha-induced protein 3 (TNFAIP3) and tumor-associated macrophages (TAMs) contribute to an immunosuppressive tumor microenvironment; however, their combined prognostic value in breast cancer metastasis has not been defined. Methods: TNFAIP3 and M2 macrophage markers (CD163 and CD206) were assessed by immunohistochemistry in 96 breast cancer surgical specimens, including 48 metastatic and 48 non-metastatic cases. Expression patterns were validated using 1,085 breast cancer samples from the GEPIA2 database. Functional studies were performed using TNFAIP3-overexpression and TNFAIP3-knockdown breast cancer cell models co-cultured with macrophages. Macrophage polarization, cytokine production, and tumor cell migration and invasion were analyzed by flow cytometry, qPCR, ELISA, and Transwell assays. Predictive performance was evaluated using multivariate logistic regression and receiver operating characteristic (ROC) analyses. Results: TNFAIP3 expression was positively correlated with CD163 ( r = 0.322, P < 0.001) and CD206 ( r = 0.370, P < 0.001) in breast tumors developing postoperative distant metastasis, with stronger correlations observed in the GEPIA2 cohort. Mechanistically, TNFAIP3 overexpression promoted CCL2 secretion, activated CCR2 signaling, and induced M2-like macrophage polarization, resulting in a 1.5- to 2.3-fold increase in tumor cell migration and invasion. Elevated TNFAIP3, CD163, and CD206 were independently associated with metastasis. TNFAIP3 alone showed good predictive performance (AUC = 0.84), while the combination of TNFAIP3 and CD163 achieved the highest accuracy (AUC = 0.90), followed by TNFAIP3 and CD206 (AUC = 0.87). Conclusions: TNFAIP3 promotes macrophage reprogramming through the CCL2/CCR2 axis, fostering a pro-metastatic tumor microenvironment in breast cancer. Combined assessment of TNFAIP3 and M2 macrophage markers provides a novel biomarker panel for postsurgical risk stratification and prognosis of metastatic relapse, supporting further prospective clinical validation.