BMB Reports最新文献

Endothelial cells (ECs) undergo endothelial-to-mesenchymal transition (EndMT) during the pathophysiology of cardiovascular diseases, a complex cellular transdifferentiation process closely associated with increased oxidative stress under adverse conditions such as myocardial infarction (MI). Decursin, a major constituent of Angelica gigas Nakai, displays diverse pharmacological properties. This study aimed to examine the antioxidant impact of decursin on EndMT regulation in both in vitro and in vivo models as a potential therapeutic strategy for MI. In vitro the inhibitory effects of decursin treatment were analyzed by measuring the expression of EndMT-associated genes, assessing endothelial function, intracellular ROS levels, and mitochondrial membrane potential. Furthermore, the study elucidated antioxidation-related signaling mechanisms within EndMT-induced ECs. In vivo, the therapeutic potential of decursin was investigated using a mouse model of MI. Decursin administration attenuated the EndMT process by upregulating CD31 and VE-Cadherin while decreasing fibronectin and α-SMA expression in EndMT-induced ECs. It also lowered ROS levels, preserved mitochondrial membrane potential, and modulated functional properties, resulting in enhanced LDL uptake and diminished endothelial permeability. Endothelial integrity was sustained via regulation of the PI3K/AKT/NF-κB and Smad-dependent signaling pathways, both responsive to oxidative stress during EndMT. In the MI mouse model, decursin reversed EndMT, lessened myocardial fibrosis and apoptosis, and promoted recovery of infarcted regions. The treated hearts demonstrated improved cardiovascular performance. Decursin represents a novel therapeutic strategy targeting intracellular oxidative stress induced by EndMT. By exerting antioxidant activity through the PI3K/AKT/NF-κB and Smaddependent pathways, decursin maintains endothelial function, suppresses myocardial fibrosis, and supports cardiac recovery following MI therapy. [BMB Reports 2025; 58(9): 406-414].

Lipid metabolism plays an important role in aging and longevity, and lipophagy-a specialized form of autophagy that targets lipid vesicles-regulates lipid homeostasis and alleviates metabolic diseases such as metabolic dysfunctionassociated steatotic liver disease (MASLD). Ilimaquinone (IQ), a sesquiterpene extracted from the sea, is well-known for its various biological effects; however, its effects on lipid metabolism and longevity have not yet been elucidated. In this study, IQ acted in a dose-dependent manner, extending the lifespan of Caenorhabditis elegans (C. elegans) by up to 50%, causing transcriptional changes in 1,878 genes related to fatty acid degradation and longevity pathways. Additionally, IQ reduced lipid accumulation in C. elegans and mouse AML12 cells, as confirmed by Oil Red O staining. RNA sequencing and quantitative reverse transcription polymerase chain reaction validation showed that the expression of key lipid metabolism genes, such as lipl-4 in worms and Lipa in mammalian cells, increased with IQ treatment. Lipophagy has been identified as the key mechanism underlying the lipid-lowering effects of IQ. The inhibition of autophagy by Bafilomycin A1 reversed the reduction in lipid accumulation in both C. elegans and AML12 cells, indicating the involvement of autophagic flux. Western blot analysis demonstrated that IQ activates AMPK, a key regulator of autophagy and lipid metabolism, and inhibits mTOR. IQ increased the turnover of LC3-II and decreased p62 levels, confirming autophagosome formations and increased lysosomal degradation. These findings suggest that IQ promotes autophagy, alleviates lipid accumulation, and has a therapeutic potential for metabolic diseases. In addition, AMPK activation and mTOR inhibition pathways may have contributed to the extension of C. elegans lifespan. Future studies should investigate the potential of IQ in lipid metabolism regulation and lifespan extension. [BMB Reports 2025; 58(9): 415-423].

Exosomes-nanoscale extracellular vesicles secreted by various cell types-play a crucial role in intercellular communication by delivering biologically active molecules, such as proteins, nucleic acids, and lipids. Due to their intrinsic biocompatibility, targeting capabilities, and stability, exosomes have emerged as promising vehicles for diagnostics and therapeutics in a wide range of diseases, including cancer, and neurodegenerative, cardiovascular, and autoimmune disorders. The ability to monitor exosome biodistribution and dynamics in vivo is pivotal to promoting their clinical translation. This review provides a comprehensive overview of the current visualization techniques employed for in vivo exosome imaging: optical imaging, magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT), positron emission tomography (PET), and emerging modalities, such as photoacoustic imaging, ultrasound, and Raman-based approaches. The advantages, limitations, and representative applications of each imaging modality are critically discussed, with emphasis on labeling strategies that enhance tracking sensitivity and specificity. Optical imaging offers high sensitivity, but is limited by shallow tissue penetration, whereas MRI provides excellent spatial resolution, but suffers from low molecular sensitivity. Radionuclide-based imaging, such as PET and SPECT, enables highly sensitive, quantitative tracking, but presents challenges regarding radiotracer stability and safety. Emerging multimodal platforms and labeling innovations are highlighted for their potential to overcome current limitations. Future research directions include the development of non-invasive, highly sensitive, and clinically translatable imaging systems, as well as standardized protocols to ensure reproducibility. Advances in exosome imaging technologies will be instrumental to unlock the full diagnostic and therapeutic potential of exosomebased platforms in precision medicine. [BMB Reports 2025; 58(8): 340-349].

Tau acetylation has been recognized as a pivotal post-translational modification associated with the pathogenesis of Alzheimer's disease (AD) and other tauopathies. This review offers a detailed synthesis of the current understanding of site-specific tau acetylation, its regulatory enzymes, and its profound impacts on tau biology. Acetylation influences tau degradation, aggregation, propagation, and microtubule-binding properties in a residue-specific manner, often in conjunction with other modifications such as phosphorylation and ubiquitination. Furthermore, this review emphasizes emerging therapeutic strategies targeting tau acetylation, including small-molecule inhibitors of p300/CBP and monoclonal antibodies against acetylated tau epitopes. While several of these approaches are currently undergoing clinical trials, many acetylation sites are still inadequately characterized, emphasizing the need for additional mechanistic studies. An enhanced understanding of tau acetylation will be vital for devising targeted therapies to halt or reverse the progression of tau-mediated neurodegeneration. [BMB Reports 2025; 58(8): 325-339].

Aurora B is a widely studied mitotic checkpoint kinase that forms a part of the chromosomal passenger complex. The entry to and exit from mitosis are exquisitely controlled by Aurora B proteins, which regulate mitotic phases including chromosomal condensation, segregation, and cytokinesis, ensuring faithful propagation of daughter cells. Abnormal regulation of Aurora B proteins during the cell cycle can cause increased chromosomal segregation errors and ultimately lead to cancer. Thus, it is important to understand the key mechanisms that can modulate Aurora B protein levels during the cell cycle. Therefore, in this study we demonstrated the role of Ubiquitin-specific protease 7 (USP7) in regulating Aurora B protein level. Aurora B protein levels are upregulated when USP7 is dose-dependently increased, and downregulated when USP7 is depleted. By co-immunoprecipitation and Duolink assays, we demonstrated that USP7 interact with Aurora B. Furthermore, by treating cycloheximide we showed that USP7 extends the Aurora B protein half-life by its deubiquitinating activity. Finally, CRISPR/Cas9-mediated USP7 knockout produces severe nuclear structural defects causing multi-nucleation and cytokinesis failures, suggesting that the important role of USP7 during mitotic progression in stabilizing Aurora B. [BMB Reports 2025; 58(8): 350-356].

Rosacea is a chronic inflammatory skin disorder characterized by facial erythema, papules, pustules, and telangiectasia, affecting approximately 5.5% of the global population. Current treatments, primarily topical and oral antibiotics and anti-inflammatories, often show limited efficacy and may cause undesirable side effects, prompting the need for alternative therapies. Cannabidiol (CBD), a non-psychoactive component of Cannabis sativa, has shown promise as a therapeutic agent for rosacea due to its anti-inflammatory, antioxidant, and anti-apoptotic properties. CBD interacts with the endocannabinoid system, which plays a crucial role in cutaneous homeostasis. This study evaluated the efficacy of CBD, both alone and in combination with metronidazole (MET), in reducing inflammation and modulating immune responses in a rosacea-like mouse model. Our results demonstrated that both CBD and MET significantly inhibited redness, epidermal thickness, and mast cell infiltration, with their combination being more effective. Mechanistic analyses revealed that the therapeutic effect of CBD is associated with the suppression of key inflammatory regulators in the MAPK signaling pathway, particularly the ERK, JNK, and p38 pathways. CBD treatment also led to a significant reduction in pro- inflammatory cytokines and chemokines, indicating immune modulation. These findings suggest that CBD, especially in combination with MET, may represent a novel therapeutic option for rosacea and offer a scientific basis for its clinical application in managing inflammatory skin conditions. [BMB Reports 2025; 58(8): 357-363].

[Erratum to: BMB Reports 2025; 58(7): 307-312, PMID: 40495489, PMCID: PMC12313400] BMB Reports recently published the article "Modulating CD226 and PD-(L)1 pathways improves CMV-specific CD8＋T cell responses in the absence of IL-2" (BMB Rep. 2025; Vol. 58, No.7, pp.307-312) by Hye-In Sim et al. The original publication inadvertently omitted two sections: ACKNOWLEDGMENTS and CONFLICT OF INTEREST. These sections have now been added to the online version. The authors and editorial office apologize for any inconvenience or confusion this omission may have caused to the authors and readers. ACKNOWLEDGMENTS This work was supported by an intramural grant from KIST and Asan Medical Center (2022IP0092-1) and by grants from the National Research Foundation of Korea (NRF) (RS-2024-00338729 to H. Jin and RS-2024-00337093 to Y. Park). CONFLICT OF INTEREST All authors declare that they have no competing interests.

CRISPR-Cas12a proteins are RNA-guided endonucleases classified as type V-A effectors that function similarly to Cas9, but possess distinct biochemical features. Previous studies have reported that compared to Cas9, Cas12a exhibits reduced off-target activity, yet the mechanistic origin of this high specificity remains unclear. In this study, we used singlemolecule fluorescence assays to investigate the kinetic basis for the reduced off-target effects of Cas12a. Introducing double mismatches at various positions within the target DNA enabled systematic analysis of the off-target effects on individual reaction steps in the Cas12a-mediated DNA cleavage reaction: seeding, stable R-loop formation, and DNA cleavage. Our results show that mismatches within a 17 bp PAM-proximal seed region significantly impair stable R-loop formation and subsequent cleavage, whereas mismatches in the PAM-distal region exert minimal or negligible effects. These results suggest that the low off-target tolerance of Cas12a and the resulting high on-target selectivity arise from the high sensitivity of the R-loop formation rate to DNA mismatches in the PAM-proximal region, which strongly correlates with cleavage efficiency. This work establishes R-loop formation as a conformational checkpoint for specific target cleavage, and provides a mechanistic framework to improve the fidelity of genome editing. [BMB Reports 2025; 58(8): 364-368].

Histone deacetylases (HDACs) are essential enzymes that play a pivotal role in the epigenetic regulation of gene expression by catalyzing the removal of acetyl groups from histone and non-histone proteins. This deacetylation is a crucial post-translational modification that influences several cellular processes, such as chromatin remodeling, transcriptional repression, and signal transduction. Recent studies have illuminated the significant involvement of HDACs in the pathogenesis of fibrotic diseases, conditions characterized by the excessive accumulation of extracellular matrix components leading to progressive organ dysfunction and failure. These diseases commonly affect the liver, kidney, heart, lung, and colon. The contribution of HDACs to fibrogenesis is multifaceted, involving the modulation of gene expression that governs inflammatory and fibrotic signaling pathways. Therefore, targeting HDACs with specific inhibitors has emerged as a promising therapeutic strategy to mitigate fibrosis in various organs. HDAC inhibitors (HDACi) can potentially reverse the aberrant gene expression profiles associated with fibrotic diseases by restoring acetylation levels, thus attenuating fibrotic responses. Several HDAC inhibitors, such as vorinostat, trichostatin A, and romidepsin, have shown efficacy in preclinical models of fibrosis, demonstrating their potential to suppress fibrogenic signaling pathways and reduce extracellular matrix deposition. In this review, we provide a comprehensive analysis of the current understanding of the roles of HDACs in the regulation of histone and non-histone proteins, and their implications for fibrotic diseases. We compare the molecular mechanisms by which different classes of HDACs contribute to fibrosis in various organs, and highlight the therapeutic potential of HDAC inhibition. This review underscores the importance of further research into HDAC-specific inhibitors as viable treatments for fibrotic diseases, aiming to develop targeted therapies that can effectively ameliorate fibrosis and improve patient outcomes. [BMB Reports 2025; 58(8): 313-324].

Glucocorticoids (GCs) are steroid hormones that are commonly utilized in clinical practice due to their immunosuppressive properties. While GCs are commonly understood to diminish various aspects of the immune response, there is evidence suggesting that they may, under certain conditions, enhance immune responses, particularly within the realm of type 2 immunity. In this mini review, we delineate the current understanding of how GCs differentially affect immune responses related to type 2 immunity, including both in vivo and in vitro-such as Th2 (T helper type 2) cell differentiation, regulatory T cell functions, immunoglobulin E production by B cells, and the roles of myeloid cells like dendritic cells, mast cells, eosinophils, and basophils. Furthermore, we probe the molecular mechanisms by which GCs selectively influence these cell types, and discuss how these insights enhance our basic understanding of GC-driven immune regulation. Unraveling these intricate, context-dependent effects could inform the development of more precise and efficacious GC-based treatments, while reducing adverse outcomes associated with Th1/Th2 imbalance, including heightened infection risks and exacerbation of allergic responses.