Breast cancer remains a leading cause of morbidity and mortality worldwide. Triple-negative breast cancer (TNBC) presents unique challenges owing to its aggressiveness and limited treatment options. Paclitaxel-based chemotherapy is widely used in breast cancer treatment. However, its efficacy is often limited by toxicity, multidrug resistance, and lack of targeted delivery. In response to these challenges, recent studies have focused on the use of extracellular vesicles (EVs), particularly plant-derived EVs, as innovative drug delivery systems capable of enhancing therapeutic outcomes and reducing adverse effects. Plant-derived EVs offer significant advantages owing to their biocompatibility, low immunogenicity, and scalability. They provide a natural platform for delivering chemotherapeutics such as paclitaxel and doxorubicin directly to tumor cells. This review explores the therapeutic potential of plant-derived EVs in breast cancer treatment, focusing on TNBC by examining their ability to improve drug stability, bioavailability, and selective targeting of cancer cells. Key studies on EVs derived from plants such as grapefruit, ginger, and tea leaves have demonstrated their capacity to deliver chemotherapeutic agents effectively while mitigating common side effects associated with conventional delivery methods. Although the use of plant-derived EVs is still in early stages of research, findings suggest that that these nanocarriers can serve as transformative tools in oncology, providing a versatile and efficient platform for precise cancer treatment. This review highlights current landscape of research on plant-derived EVs, their application in breast cancer therapy, and future directions required to translate these findings into clinical practice.

Programmed cell death 5 (PDCD5) regulates cell death and suppresses tumor progression. Since the stability and nuclear translocation of PDCD5 are regulated by TP53-dependent cell death stimuli, knowledge of the regulatory mechanism of PDCD5 function is required to better understand the TP53-signaling pathway. We identified Jumonji domain-containing protein 4 (JMJD4) to be a PDCD5-interacting protein using liquid chromatography-mass spectrometry (LC-MS). Interestingly, JMJD4 upregulates cell proliferation and chemo-resistance under genotoxic stress conditions by colony-formation assay and decreases TP53-related apoptotic genes (BAX, PUMA) by suppressing protein levels of PDCD5. Additionally, using the Cancer Genome Atlas and the Gene Expression Omnibus database to confirm the clinical correlation between JMJD4 and cancer patients, we verified that JMJD4 is associated with a poor prognosis in colon cancer and lung cancer patients. Therefore, this study demonstrates that JMJD4 directly interacts with PDCD5, regulates cancer cell death negatively, and could be a potential therapeutic target for cancer development.

Prime editing is widely used in many organisms to introduce site-specific sequence modifications such as base substitutions, insertions, and deletions in genomic DNA without generating double-strand breaks. Despite wide-ranging applications of prime editing, prime editors (PEs) have low editing efficiencies, especially in dicot plants. Therefore, PEs are barely used for genome engineering in dicot plant species. Here, based on previous approaches used to improve prime editing efficiency, we generated different combinations of PE components and prime editing guide RNAs (pegRNAs) and examined their prime editing efficiencies in Arabidopsis thaliana protoplasts as a dicot model system. We found that v4e2, in which PE was fused to viral nucleocapsid (NC) protein, RNase H-deleted M-MLV RT, and a dominant negative version of human mutL homolog 1 (hMLH1dn), showed the highest prime editing efficiency in Arabidopsis protoplasts when it was co-transfected with dual enhanced pegRNA. Our results suggest that the v4e2 PE system could be used for efficient prime editing in dicot plants.

Many studies on osteoblasts have suggested that Wnt5a plays a crucial role in excessive osteoblast activity, which is responsible for ectopic new bone formation, but research on osteoclasts in ankylosing spondylitis (AS) remains relatively limited. This study aimed to explore whether Wnt5a influences osteoclast-mediated bone resorption in curdlan-injected SKG mice, a model that mimics AS. Compared to the Vehicle group, the Wnt5a treatment group exhibited statistically higher clinical arthritis scores and increased hindpaw thickness values. Micro-computed tomography (microCT) analysis of hindpaws revealed a significant increase in inflamed and ectopic bone density in the Wnt5a-treated group compared to the Vehicle group. Histological examination also showed pronounced inflammation and structural bone damage in the bone marrow of ankles in the Wnt5a-treated group. Intriguingly, microCT analysis of the femur revealed that trabecular bone loss was markedly observed in the Wnt5a-treated group. Both the number of TRAP-positive osteoclasts and their activity were statistically greater in the Wnt5a-treated group compared to the Vehicle group. Serum markers of bone resorption, but not bone formation, were also significantly elevated in the Wnt5a-treated group. Notably, promotion of osteoclast differentiation by Wnt5a was inhibited following treatment with anti-Wnt5a. These findings suggest that targeting Wnt5a could be a promising strategy for mitigating pathological bone features in AS by modulating osteoclast activity.

Trichomonas vaginalis is an extracellular flagellated protozoan responsible for trichomoniasis, one of the most prevalent nonviral sexually transmitted infections. To persist in its host, T. vaginalis employs sophisticated gene regulation mechanisms to adapt to hostile environmental conditions. Although transcriptional regulation is crucial for this adaptation, the underlying molecular mechanisms remain poorly understood. Epigenetic regulation, particularly histone modifications, has emerged as a key modulator of gene expression. A previous study demonstrated that histone modifications, H3K4me3 and H3K27ac, promote active transcription. However, the complete extent of epigenetic regulation in T. vaginalis remains unclear. The present study extended these findings by exploring the repressive role of two additional histone H3 modifications, H3K9me3 and H3K27me3. Genome-wide analysis revealed that these modifications negatively correlated with gene expression, affecting protein-coding and transposable element genes (TEGs). These findings offer new insights into the dual role of histone modifications in activating and repressing gene expression and provide a more comprehensive understanding of epigenetic regulation in T. vaginalis. This expanded knowledge may inform the development of novel therapeutic strategies targeting the epigenetic machinery of T. vaginalis.

A type of programmed cell death called ferroptosis is defined by increased iron-dependent lipid peroxidation. Mitochondria play a central role in iron metabolism. Mitochondrial defects include decreased cristae density, membrane rupture, and decreased mitochondrial membrane density, which occur as a result of ferroptosis. One of the important regulator of mitochondrial biogenesis is PGC1α. While recent studies have begun to explore the association between PGC1α and ferroptosis, the specific role of PGC1α in erastin-induced mitochondrial dysfunction during ferroptotic cell death has not been fully elucidated. In this study, we demonstrate for the first time that PGC1α is a key regulator of erastin-induced mitochondrial-dependent lipid peroxidation and dysfunction during ferroptosis in HT1080 fibrosarcoma cells. In this study, we examined PGC1α function in ferroptosis. Erastin, an inducer of ferroptosis, boosted the expression of PGC1α. Moreover, PGC1α down-regulation reduced erastin-induced ferroptosis. The most important biochemical feature of ferroptosis is the increase in iron ion (Fe²⁺)-dependent lipid peroxide (LOOH) concentration. Mitochondrial-dependent lipid peroxidation was abolished by PGC1α downregulation. In addition, PGC1α was induced during mitochondrial dysfunction in erastin-induced ferroptosis. Mitochondrial membrane potential loss and mitochondrial ROS production associated with erastin-induced mitochondrial dysfunction were blocked by PGC1α inhibition. In addition, erastin-induced lipid peroxidation in HT1080 fibrosarcoma cells was regulated by PGC1α inhibitor. This phenomenon was also consistent in HT1080 cells transfected with PGC1α shRNA. Taken together, these results suggest that PGC1α is a key factor in erastin-induced mitochondrial-dependent lipid peroxidation and dysfunction during ferroptosis cell death.

Understanding molecular characteristics and metabolic processes of the mammalian endometrium is crucial for advancing biological research, particularly in veterinary obstetrics and pathology. This study established and analyzed organoids from endometrial epithelial stem cells of five mammals with different placental types: cows (cotyledonary), dogs and cats (zonary), pigs (diffuse), and rats (discoid). Organoids from these five species were maintained for over 13 passages, frozen, and thawed. Pathological analysis confirmed that they retained characteristics of their original tissues. Furthermore, integrative transcriptome analysis of organoids and tissues from the five species highlighted key pathways such as PI3K-Akt signaling and extracellular matrix-receptor interaction known to be crucial in cancer research. Although genes associated with vascular smooth muscle contraction were downregulated, these organoids exhibited significant activities of genes involved in hormone metabolism. In conclusion, our study achieved stable establishment of endometrial organoids from five mammals with different placental types, offering foundational data for organoid research. In the future, these organoids are suitable models for investigating uterine physiology and diseases and for developing potential therapies.