BMB Reports最新文献

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. [BMB Reports 2025; 58(2): 95-103].

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 plantderived 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. [BMB Reports 2025; 58(2): 53-63].

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 osteoclastmediated 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. [BMB Reports 2025; 58(2): 75-81].

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. [BMB Reports 2025; 58(2): 89-92].

[Erratum to: BMB Reports 2024; 57(11): 497-502, PMID: 39384175, PMCID: PMC11608851] The BMB Reports would like to issue a correction to an article published in BMB Rep. 57(11): 497-502, titled "Differential roles of N- and C-terminal LIR motifs in the catalytic activity and membrane targeting of RavZ and ATG4B proteins". The original acknowledgment contained incorrect grant information. This has now been corrected at the authors' request as follows: The work was supported by the Science Research Center Program of the National Research Foundation NRF (2020R1A5A1019023); Neurological Disorder Research Program of the NRF (2020M3E5D9079911); Basic research program of the NRF (2023R1A2C2007082) to JAL. D.-J.J. was supported by the Basic Research Program of NRF (2022R1F1A1066552), and the NRF grant funded by the Korea government (MSIT) (RS-2023-00218515). Specifically, the grant number has been updated from [2023R1A2C2008092] to [2023R1A2C2007082]. The authors apologize for any inconvenience or confusion this error may have caused. The ACKNOWLEDGEMENTS section in the original PDF version has been updated accordingly.

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. [BMB Reports 2025; 58(2): 82-88].

CRISPR/Cas systems have emerged as powerful tools for gene editing, nucleic acid detection, and therapeutic applications. Recent advances in single-molecule techniques have provided new insights into the DNA-targeting mechanisms of CRISPR/ Cas systems, in particular, Types I, II, and V. Here, we review how single-molecule approaches have expanded our understanding of key processes, namely target search, recognition, and cleavage. Furthermore, we focus on the dynamic behavior of Cas proteins, including PAM site recognition and R-loop formation, which are crucial to ensure specificity and efficiency in gene editing. Additionally, we discuss the conformational changes and interactions that drive precise DNA cleavage by different Cas proteins. This mini review provides a comprehensive overview of CRISPR/Cas molecular dynamics, offering conclusive insights into their broader potential for genome editing and biotechnological applications. [BMB Reports 2025; 58(1): 8-16].

The nucleosome is the fundamental structural unit of chromosome fibers. DNA wraps around a histone octamer to form a nucleosome while neighboring nucleosomes interact to form higher-order structures and fit gigabase-long DNAs into a small volume of the nucleus. Nucleosomes interrupt the access of transcription factors to a genomic region and provide regulatory controls of gene expression. Biochemical and physical cues stimulate wrapping-unwrapping and condensation-decondensation dynamics of nucleosomes and nucleosome arrays. Nucleosome dynamics and chromatin fiber organization are influenced by changes in the ionic background within the nucleus, post-translational modifications of histone proteins, and DNA sequence characteristics, such as histone-binding motifs and nucleosome spacing. Biochemical and biophysical measurements, along with in silico simulations, have been extensively used to study the regulatory effects on chromatin dynamics. In particular, single-molecule measurements have revealed novel mechanistic details of nucleosome and chromatin dynamics. This minireview elucidates recent findings on chromatin dynamics from these approaches. [BMB Reports 2025; 58(1): 24-32].

Single-molecule techniques allow researchers to investigate individual molecules and obtain unprecedented details of the heterogeneous nature of biological entities. They play instrumental roles in studying DNA-protein interactions due to the ability to visualize DNA or proteins and to manipulate individual DNA molecules by applying force or torque. Here, we describe single-molecule DNA-flow stretching assays as hybrid tools that combine forces with fluorescence. We also review how widely these assays are utilized in elucidating working mechanisms of DNA-binding proteins. Additionally, we provide a brief explanation of various efforts to prepare DNA substrates with desired internal protein-binding sequences. More complicated needs for DNA-protein interaction research have led to improvements in single-molecule DNA flow-stretching techniques. Several DNA flow-stretching variants such as DNA curtain, DNA motion capture assays, and protein-induced fluorescence enhancement (PIFE) are introduced in this mini review. Singlemolecule DNA flow-stretching assays will keep contributing to our understanding of how DNA-binding proteins function due to their multiplexed, versatile, and robust capabilities. [BMB Reports 2025; 58(1): 41-51].

Model membrane systems have emerged as essential platforms for investigating membrane-associated processes in controlled environments, mimicking biological membranes without the complexity of cellular systems. However, integrating these model systems with single-molecule techniques remains challenging due to the fluidity of lipid membranes, including undulations and the lateral mobility of lipids and proteins. This mini-review explores the evolution of various model membranes ranging from black lipid membranes to nanodiscs and giant unilamellar vesicles as they adapt to accommodate electrophysiology, force spectroscopy, and fluorescence microscopy. We highlight recent advancements, including innovations in force spectroscopy and single-molecule imaging using free-standing lipid bilayers, and the development of membrane platforms with tunable composition and curvature for improving fluorescence-based studies of protein dynamics. These integrated approaches have provided deep insights into ion channel function, membrane fusion, protein mechanics, and protein dynamics. We highlight how the synergy between single-molecule techniques and model membranes enhances our understanding of complex cellular processes, paving the way for future discoveries in membrane biology and biophysics. [BMB Reports 2025; 58(1): 33-40].