BMB Reports最新文献

{"title":"Mitochondrial transfer from human embryonic stem cell-derived mature cardiomyocytes to mesenchymal stem cells.","authors":"Ye Seul Kim, Dasol Kim, Yoon Ji Jung, Jung Won Yoon, Yong Seong Kwon, Seong-Jang Kim, Jae Ho Kim","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Mitochondria are crucial for energy metabolism and their dysfunction is implicated in the development of various human diseases. Direct mitochondrial transplantation has shown potential in reversing mitochondrial dysfunction in recipient cells. Mesenchymal stem cells (MSCs) present a promising approach as donor cells for such transplantation. We have previously demonstrated that tomatidine, a natural steroidal alkaloid, promotes the differentiation of human embryonic stem cells (hESCs) into mature cardiomyocytes by enhancing mitochondrial quantity and function. In this study, we assessed the capacity of hESCderived cardiomyocytes (hESC-CMs) and MSCs as donor cells for mitochondrial transplantation. Mitochondria were extracted from MSCs, immature hESC-CMs, and tomatidine-treated mature hESC-CMs. Treating MSCs with mitochondria derived from mature hESC-CMs led to a marked increase in mitochondrial protein levels, such as COX IV and MIC60, in the recipient MSCs, in comparison to those receiving mitochondria from immature hESC-CMs or MSCs. Transplantation of mature hESC-CM-derived mitochondria significantly enhanced the proliferation of recipient MSCs. These findings indicate that mature hESC-CMs are highly effective as donor cells for mitochondrial transplantation in addressing mitochondrial dysfunction.</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145556312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pluripotent stem cell-derived chimeric antigen receptor-natural killer cells targeting epidermal growth factor receptor 2 for cancer immunotherapy.","authors":"Jongsuk Han, Chaeyeon Jin, Sae-Byeok Hwang, In Jee Lee, Young Seok Baek, Daun Jung, Ki Yeon Kim, Shoukhrat Mitalipov, Ji Hyang Kim, Hee Jung An, Yeonmi Lee, Eunju Kang","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Chimeric antigen receptor-natural killer (CAR-NK) cells are emerging as a promising platform for allogeneic, cell-based immunotherapy. Among available sources, NK cells derived from pluripotent stem cells (PSCs) provide a renewable and scalable option that overcomes the limitations of primary NK cells. Human epidermal growth factor receptor 2 (HER2), a membrane protein frequently overexpressed in many solid tumors, is an attractive target for cancer immunotherapy. In this study, we designed a green fluorescent protein (GFP)-linked anti-HER2 CAR construct and introduced it into PSCs via lentiviral transduction. Three stable PSC-derived clones (CAR-A, CAR-B, and CAR-C) were established, each co-expressing anti-HER2 CAR with GFP. After differentiation under xeno-free and feeder-free culture conditions, CAR expression was maintained in NK cells. The resulting PSC-derived CAR-NK cells displayed phenotypic and functional features comparable to wild-type PSC-derived NK cells, while showing markedly enhanced cytotoxicity against HER2-positive cancer cell lines. These findings demonstrated the potential of the use of PSC-derived anti-HER2 CAR-NK cells as a robust and scalable immunotherapy. In addition, this platform could be extended to produce CAR-NK cells directed against a wide range of tumorassociated antigens. [BMB Reports 2025; 58(11): 475-483].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"475-483"},"PeriodicalIF":3.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12665497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145408107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward unraveling molecular grammars for dsRNA-binding proteins: substrate recognition to binding mechanisms.","authors":"Jaemin Jeon, Yoosik Kim","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Long double-stranded RNAs (dsRNAs) are recognized by innate immune response proteins, thereby initiating the integrated stress response. As these RNAs adopt an A-form helical structure, immune sensors recognize dsRNAs primarily based on their structural features, such as the length of the doublestranded stretch and the triphosphate at the 5' end, rather than on specific sequences. This structure-dependent, sequenceindependent mode of RNA recognition is also characteristic of many dsRNA-binding proteins (dsRBPs). Consequently, multiple dsRBPs share a common pool of dsRNA substrates, leading to a complex regulatory network in which proteins modulate each other's activation status and signaling activities. With the development of advanced analytical techniques capable of studying RNA sequences and structures at single-nucleotide resolution, research into dsRNA-protein interactions has advanced significantly. This review discusses the long dsRNAinteracting dsRBPs encoded in the human genome, their RNA substrates, recognition mechanisms, and the downstream effects of protein-RNA interactions, with the aim of deepening our understanding of dsRNA recognition and signaling. [BMB Reports 2025; 58(11): 451-466].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"451-466"},"PeriodicalIF":3.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12665498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alloxan attenuates glucosamine-induced NF-κB activation and proinflammatory gene expression under normoglycemic conditions.","authors":"Sang-Min Kim, Chanhaeng Lee, Dong Yeol Kim, Inn-Oc Han","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Glucosamine (GlcN), a critical substrate in the hexosamine biosynthetic pathway, is known to modulate inflammatory responses in macrophages depending on extracellular glucose concentration. In hyperglycemic conditions (25 mM glucose), GlcN suppresses the production of nitric oxide (NO) and decreases the expression of inducible nitric oxide synthase (iNOS). Conversely, under normoglycemic conditions (5 mM glucose), GlcN paradoxically enhances lipopolysaccharide (LPS)-induced iNOS expression, NO production, and the upregulation of additional proinflammatory mediators. In this study, we examined the effect of alloxan, a known O-GlcNAc transferase (OGT) inhibitor, on GlcN- and/or LPS-mediated inflammatory responses in RAW264.7 macrophage cells. Under hyperglycemic conditions, alloxan exhibited little effect on the LPS-induced or LPS plus GlcN-induced expression of iNOS, cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). In contrast, under normoglycemic conditions, alloxan significantly inhibited the induction of these inflammatory genes in response to LPS plus GlcN. At the mechanistic level, alloxan reduced NF-κB DNA-binding activity and prevented its recruitment to the iNOS promoter. In addition, alloxan attenuated GlcN-induced increase in OGlcNAcylation of the NF-κB subunit p65. Collectively, these results indicate that OGT-mediated O-GlcNAcylation of NF-κB is critical for GlcN-induced proinflammatory signaling under normoglycemia. Our work highlights the glucose dependency of O-GlcNAc cycling in macrophage responses and provides new perspectives on the metabolic regulation of innate immune responses. [BMB Reports 2025; 58(11): 467-474].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"467-474"},"PeriodicalIF":3.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12665496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145407903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N-acetyl-L-alanine ameliorates atopic dermatitis-like symptoms by suppressing Th2 differentiation in DNFB-induced NC/Nga mice.","authors":"Uyanga TSogt, Seung-Gook Kim, Suhong Duan, Hyung-Jin Lim, Jiaying Bao, Hwa-Ryung Song, Jong-Suk Kim, Myung-Kwan Han","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Atopic dermatitis (AD) is a chronic dermatological disorder characterized by intense pruritus and eczematous lesions. Repeated topical application of 2,4-dinitrofluorobenzene (DNFB) in NC/Nga mice produces AD-like clinical symptoms that closely resemble human AD. N-acetyl-L-alanine (L-NAA), a derivative of L-Alanine, has unknown biological and physiological effects on cutaneous tissue. In this study, we investigated whether L-NAA modifies AD-like symptoms elicited by ongoing DNFB exposure in NC/Nga mice. Topical administration of L-NAA markedly attenuated the development of AD-like cutaneous lesions triggered by DNFB. L-NAA treatment further suppressed DNFB-induced infiltration of eosinophils and mast cells and prevented the increase of serum IgE resulting from DNFB application. L-NAA treatment decreased DNFB-stimulated expression of IL-4, a Th2-associated cytokine, but increased IFN-γ expression, indicative of Th1 activity, within the skin lesions. In addition, L-NAA prevented the DNFB-driven upregulation of GATA3, a central regulator of Th2 lineage differentiation, in CD4＋ cells, with no effect on T-bet, the principal regulator of Th1 cells. These findings indicate that L-NAA can limit Th2 differentiation in the AD mouse model. Therefore, L-NAA may serve as a promising therapeutic and immunomodulatory compound against AD. [BMB Reports 2025; 58(10): 437-443].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"437-443"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12576411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145013802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional analysis of secreted tissue inhibitor of metalloproteinases-1 from adult human neural stem cells (ahNSCs) for regeneration and neuroprotection.","authors":"Ki Hoon Kim, Dong Geun Hong, Hye Yun Chae, Dong Oh Kim, So Heun Lee, Chung Kwon Kim, Geun-Hyoung Ha, Kyeung Min Joo","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The adult human neural stem cell (ahNSC)-conditioned medium (CM) contains various secreted factors that promote tissue repair and neuroprotection. This study aimed to identify the key secreted proteins in ahNSC-CM and investigate the role of tissue inhibitor of metalloproteinases-1 (TIMP-1) in wound healing, angiogenesis, and neuroprotection against oxygenglucose deprivation. Cytokine array and liquid chromatography- tandem mass spectrometry analysis of ahNSC-CM revealed that monocyte chemoattractant protein-1 (MCP-1) and TIMP-1 were highly abundant. Enzyme-linked immunosorbent assay confirmed the enrichment of both in ahNSC-CM. Recombinant human TIMP-1 promoted wound closure and angiogenesis, whereas neutralizing TIMP-1 in ahNSC-CM attenuated these effects, with wound healing involving the extracellular signalregulated kinases 1 and 2 and protein kinase B pathways. Furthermore, ahNSC-CM protected neurons from oxygen-glucose deprivation-induced apoptosis, and this neuroprotective effect was partially reversed by TIMP-1 neutralization, potentially through the modulation of B-cell lymphoma 2 and B-cell lymphoma 2-associated X protein expression. Consistent with findings in ahNSCs, where monocyte chemoattractant protein-1 is highly expressed and contributes to pro-angiogenic effects, our study highlights the importance of secreted factors such as TIMP-1 in the therapeutic potential of ahNSC-CM. These findings suggest that TIMP-1 is a significant component of ahNSC-CM and contributes to its regenerative and neuroprotective properties. [BMB Reports 2025; 58(10): 444-449].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"444-449"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12576409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145013769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systems memory consolidation during sleep: oscillations, neuromodulators, and synaptic remodeling.","authors":"Jaekyung Kim, Minjeong Park","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Memory consolidation transforms newly acquired experiences into stable long-term memories essential for learning and cognition. This process involves systems consolidation, where memory traces are reorganized across brain regions, and synaptic consolidation, which fine-tunes local neural connections. Sleep plays a critical role in both, coordinating memory reactivation, synaptic remodeling, and long-range neural communication. Systems consolidation is supported by stagespecific brain oscillations: during NREM sleep, the coupling of slow-oscillations, spindles, and sharp-wave ripples facilitates hippocampal-cortical transfer of memory representations, while REM sleep theta oscillations contribute to memory integration, abstraction, and emotional tagging. Complementary neuromodulatory dynamics, particularly involving norepinephrine and dopamine, regulate the timing and prioritization of memory processing. At the synaptic level, sleep balances strengthening and weakening of connections through a coordinated interplay of NREM and REM activity. Recent findings also suggest that dreaming may reflect the subjective correlate of these processes, particularly through the integration of recent and remote memory fragments. Although the precise relationship between systems-level reorganization and local synaptic refinement remains unclear-partly due to current technical limitations-emerging approaches are beginning to bridge these scales. Together, these findings underscore the integrative role of sleep in optimizing memory consolidation and offer promising avenues for clinical and translational research. [BMB Reports 2025; 58(10): 425-436].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"425-436"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12576410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Redefining preclinical testing: human-relevant alternatives beyond animal models.","authors":"Jieun Jang, Wonjun Yang, Hanseul Jeong, Nam-Kyung Lee, Jong-Gil Park, Wantae Kim, Boksik Cha, Sung-Jin Yoon, Ji-Yoon Noh, Jangwook Lee","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Both ethical imperatives and scientific limitations increasingly challenge the traditional reliance on animal models for toxicity testing and drug evaluation, particularly in the era of precision medicine. In response, a paradigm shift is underway, marked by the development of advanced in vitro and in silico technologies that can offer human-relevant and mechanistically informed alternatives. This review examines well-established alternatives, such as receptor binding assays, the monocyte activation test, and enzyme-linked immunosorbent assays, highlighting their applications, mechanisms, and limitations. We further explore emerging human-relevant technologies that include organoids, organ-on-a-chip systems, microphysiological systems, and artificial intelligence-powered modeling platforms. Special emphasis is placed on immune-integrated microphysiological systems as next-generation platforms to evaluate immunotherapy, vaccine responses, and immune toxicities. These models recapitulate dynamic human physiological processes, such as hematopoiesis and germinal center reactions, beyond the capabilities of traditional animal systems. Collectively, these technologies represent scientifically superior and ethically progressive trajectories for preclinical testing. Their integration into regulatory and industrial workflows requires continued refinement, cross-sector collaboration, and standardization.</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roles of RNA modifications in aging and age-related diseases.","authors":"Eunseok Kang, Rosa Haque, Hanseul Lee, Seung-Jae V Lee","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>RNA modifications are key epigenetic alterations that play regulatory functions in RNA biology, including RNA stability and translation. Emerging evidence indicates that RNA modification is crucial for various physiological and pathological processes, including aging. This review describes functions of key RNA modifications, including N⁶-methyladenosine (m⁶A), 5-methylcytosine (m⁵C), N⁷-methylguanosine (m⁷G), 2'-O-methylation (Nm), N¹-methyladenosine (m¹A), adenosine-to-inosine (A-to-I) RNA editing, pseudouridylation (ψ), and N4-acetylcytidine (ac4C), highlighting their roles in aging and age-associated diseases. We also discuss dynamics of RNA modifications and associated protein factors during aging. This review provides important information on molecular mechanisms underlying aging regulation, focusing on effects of RNA modifications, which can help us understand healthy longevity in humans. [BMB Reports 2025; 58(9): 389-396].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"389-396"},"PeriodicalIF":3.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12481284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ubiquitination and ubiquitin-like modifications in metabolic dysfunction-associated steatotic liver disease: mechanisms and implications.","authors":"Hyunjin Rho, Uijin Kim, Jaewhan Song","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a complex metabolic disorder that encompasses a spectrum of conditions, from simple hepatic steatosis to metabolicassociated steatohepatitis (MASH). MASH is characterized by inflammation and accelerated fibrosis progression, which can ultimately lead to cirrhosis and hepatocellular carcinoma. Given its steadily increasing prevalence, MASLD has emerged as a global health epidemic. Significantly, MASLD represents a stage where liver function can still be partially restored through dietary interventions and physical exercise. However, the longterm sustainability of these lifestyle changes poses a significant challenge. Furthermore, the complex and heterogeneous nature of MASH complicates the development of pharmacotherapeutic strategies and the identification of reliable biomarkers for effective treatment. Therefore, it is essential to gain a comprehensive understanding of the molecular mechanisms driving MASLD and to develop targeted therapeutic interventions. Recent studies have underscored the critical role of posttranslational modifications (PTMs) of proteins in regulating MASLD. PTMs, such as ubiquitination, SUMOylation, Neddylation, and UFMylation, are known to modulate protein function and diverse cellular processes. Among these, ubiquitination is particularly noteworthy for its dual role in mediating protein degradation through the ubiquitin-proteasome system and in regulating cellular signaling pathways in a non-proteolytic manner, depending on the specific linkages formed at the seven distinct lysine residues (K6, K11, K27, K29, K33, K48, and K63) and the Met1-linked (M1) linear ubiquitin chain. Despite significant progress in this area, studies focusing on linkage-specific ubiquitination events that regulate MASLD remain relatively limited. Thus, this review aims to provide a comprehensive summary of the role of linkage-specific ubiquitination in regulating MASLD, as well as exploring other ubiquitinlike modifications that may contribute to its pathophysiology. [BMB Reports 2025; 58(9): 371-388].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"371-388"},"PeriodicalIF":3.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12481283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}