Eun Ji Yeo, Min Jea Shin, Gi Soo Youn, Jung Hwan Park, Hyeon Ji Yeo, Hyun Jung Kwon, Yeon Joo Choi, Lee Re Lee, Na Yeon Kim, Su Yeon Kwon, Su Min Kim, Keun Wook Lee, Jong Kook Park, Chan Hee Lee, Dae Won Kim, Duk-Soo Kim, Won Sik Eum, Soo Young Choi
{"title":"Tat-GSTpi suppresses inflammatory responses by regulating ROS/MAPKs/apoptosis signaling pathways.","authors":"Eun Ji Yeo, Min Jea Shin, Gi Soo Youn, Jung Hwan Park, Hyeon Ji Yeo, Hyun Jung Kwon, Yeon Joo Choi, Lee Re Lee, Na Yeon Kim, Su Yeon Kwon, Su Min Kim, Keun Wook Lee, Jong Kook Park, Chan Hee Lee, Dae Won Kim, Duk-Soo Kim, Won Sik Eum, Soo Young Choi","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Glutathione S-transferase pi (GSTpi) is a phase II detoxifying enzyme that plays key roles in cellular processes. In a previous study, we have reported that cell permeable Tat-GSTpi can protect dopaminergic neurons against cell death. However, the precise roles of GSTpi in inflammation remain to be elucidated. Thus, the objective of present study is to investigate the one of plausible protective mechanism involved anti-inflammatory effect of GSTpi using lipopolysaccharide (LPS)- and 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced macrophages and an animal model. It was revealed that cell permeable Tat-GSTpi fusion protein markedly reduced reactive oxygen species (ROS) and DNA injury in LPS-treated cells and transduced protein showed not only inhibition of the regulation of mitogen-activated protein kinase (MAPK) and Caspase-9, but also decrease of COX-2 and iNOS expressions. Furthermore, Tat-GSTpi ameliorated skin inflammation in an animal model by inhibition the COX-2, iNOS expression and cytokines. Those results indicate that GSTpi plays a role in antagonizing LPS- and TPA-induced inflammation, suggesting GSTpi has the potential to serve as a therapeutic treatment for inflammatory related diseases.</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265148","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":"mTORC1 and STAT3 signaling are indispensable for in vitro TGFβ1-dependent three-dimensional (3D) tendon constructs.","authors":"Bon-Hyeock Koo, Aiden Smith, Kyu Sang Joeng","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Transforming Growth Factor-β1 (TGFβ1) is an established growth factor that regulates tenocyte differentiation, extracellular matrix production, and cell fate. We previously demonstrated its pivotal role in in vitro 3D tendon constructs formation; however, the downstream signaling mechanisms remain elusive. In this study, we explore the roles of mTORC1 (Mammalian Target of Rapamycin Complex 1) and STAT3 (Signal Transducer and Activator of Transcription 3) in mediating TGFβ1-induced 3D tendon formation using rapamycin (an mTORC1 inhibitor) and stattic (a STAT3 inhibitor). Inhibition of either pathway compromised TGFβ1-induced thickening of the tendon construct, cellular proliferation, and collagen fibrillogenesis. Molecular analyses revealed that mTORC1-STAT3 signaling partially mediates TGFβ1-induced Scx expression and tenocyte elongation in the peripheral layer of 3D tendon constructs. Moreover, TGFβ1 treatment augmented mTOR and STAT3 phosphorylation, while inhibition of mTORC1 signaling attenuated TGFβ1-induced STAT3 phosphorylation. These findings underscore the TGFb1-mTORC1- STAT3 signaling pathway as integral to 3D tendon constructs. Overall, our study identifies the mTORC1-STAT3 axis as a crucial mediator of TGFβ1-driven in vitro tendon formation, highlighting its importance in tendon maturation and extracellular matrix organization.</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265145","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}
Jiho Lee, Hye-Lim Mo, Yoon Ha, Dong Yeon Nam, Geumnim Lim, Jeong-Woon Park, Seoyoung Park, Woo-Young Choi, Hyun Ji Lee, Je-Keun Rhee
{"title":"Unraveling the three-dimensional genome structure using machine learning.","authors":"Jiho Lee, Hye-Lim Mo, Yoon Ha, Dong Yeon Nam, Geumnim Lim, Jeong-Woon Park, Seoyoung Park, Woo-Young Choi, Hyun Ji Lee, Je-Keun Rhee","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The study of chromatin interactions has advanced considerably with technologies such as high-throughput chromosome conformation capture (Hi-C) sequencing, providing a genome-wide view of physical interactions within the nucleus. These techniques have revealed the existence of hierarchical chromatin structures such as compartments, topologically associating domains (TADs), and chromatin loops, which are crucial in genome organization and regulation. However, identifying and analyzing these structural features require advanced computational methods. In recent years, machine learning approaches, particularly deep learning, have emerged as powerful tools for detecting and analyzing structural information. In this review, we present an overview of various machine learning-based techniques for determining chromosomal organization. Starting with the progress in predicting interactions from DNA sequences, we describe methods for identifying various hierarchical structures from Hi-C data. Additionally, we present advances in enhancing the chromosome contact frequency map resolution to overcome the limitations of Hi-C data. Finally, we identify the remaining challenges and propose potential solutions and future directions. [BMB Reports 2025; 58(5): 203-208].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"203-208"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12123201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584426","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}
Jinyoung Kim, Barsha Deshar, Min Hwang, Chandani Shrestha, Eunhye Ju, Bum-Ho Bin, Jiyoon Kim
{"title":"Quantum molecular resonance ameliorates atopic dermatitis through suppression of IL36G and SPRR2B.","authors":"Jinyoung Kim, Barsha Deshar, Min Hwang, Chandani Shrestha, Eunhye Ju, Bum-Ho Bin, Jiyoon Kim","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Atopic dermatitis (AD) is a chronic, pruritic skin disease characterized by inflammation and skin lesion cornification. While the use of corticosteroids like dexamethasone (DXM), an antiinflammatory drug, improves symptoms temporarily and quickly, this use is not a cure. Thus, we aimed to identify a new therapeutic strategy for AD using quantum molecular resonance (QMR), a novel non-invasive technique with an electromagnetic field-based therapeutic approach as an alternative to pain killers. An AD mouse model presenting AD-like skin lesions was generated by treating BALB/c mice with dinitrochlorobenzene (DNCB), and then DNCB-induced AD mice were administered DXM or QMR, and the change of AD-like skin lesions was observed. QMR ameliorated AD-like skin lesions in DNCB-induced AD mice and reduced the numbers of infiltrated mast cells and macrophages in mouse skin. QMR also alleviated thickening of the epidermis and restored integrity of the epidermal basement membrane. Several genes regulated by DNCB and counterregulated by QMR were identified through transcriptome analysis in mouse skin, and RNA silencing experiments on these genes in TNF-α/IFN-γ- or DNCB-treated human keratinocytes revealed that IL36G and SPRR2B play important roles in inflammation and keratinization. The expression of IL36G and SPRR2B was significantly reduced by QMR in skin of DNCB-induced AD mice. These results underscore the promising role of QMR in ameliorating AD characterized by inflammation and skin lesion hyperkeratosis via targeting IL36G and SPRR2B. [BMB Reports 2025; 58(5): 209-216].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"209-216"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12123202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930680","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}
Mihee Oh, Sunha Lee, Eunhye Kim, Yewon Jang, Baek-Soo Han
{"title":"VCAM1-mediated regulation of dopaminergic neuron function in Parkinson's disease.","authors":"Mihee Oh, Sunha Lee, Eunhye Kim, Yewon Jang, Baek-Soo Han","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Parkinson's disease (PD), the second most common neurodegenerative disorder, is characterized by the degeneration of dopaminergic neurons, striatal dopamine deficiency, and the accumulation of intracellular α-synuclein aggregates. This study employed induced pluripotent stem cell (iPSC) technology to generate dopaminergic neurons from somatic cells of both PD patients and healthy controls. The results demonstrate that patient-derived neurons show elevated expression of vascular cell adhesion molecule 1 (VCAM1), which correlates with altered synaptic plasticity, mitochondrial dysfunction, and impaired Rac1 and FAK2 signaling. These findings suggest that VCAM1 plays a pivotal role in PD pathogenesis, and may serve as a potential therapeutic target. [BMB Reports 2025; 58(5): 217-223].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"217-223"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12123205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770927","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":"Deubiquitinase dynamics: methodologies for understanding substrate interactions.","authors":"Sang-Ah Park, Ji Min Lee","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Deubiquitinases (DUBs) are essential regulators of protein homeostasis that influence cellular signaling, protein stability, and degradation by removing ubiquitin chains from substrate proteins. Understanding DUB-substrate interactions is critical to elucidate their functional roles and therapeutic potential. This review highlights key methodologies to investigate DUB activity and substrate interactions, including biochemical assays, fluorescence-based approaches, and in vitro deubiquitination assays. Biochemical methods, such as those measuring protein degradation rates, ubiquitination dynamics, and protein-protein interactions, provide valuable insights into DUB function and specificity. Fluorescence-based techniques that include photoconvertible reporters, fluorescent timers, and FRET enable the realtime monitoring of DUB dynamics and substrate turnover in live cells. Furthermore, in vitro deubiquitination assays provide direct mechanistic insights into DUB activity on target substrates. While each method provides unique insights, they also present challenges, like limited specificity or sensitivity, technical difficulties, or insufficient physiological relevance. Integrating complementary approaches can enhance accuracy and provide deeper insights into DUB-substrate interactions, facilitating the development of DUB-targeted therapeutic strategies. [BMB Reports 2025; 58(5): 191-202].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"191-202"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12123204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584422","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}
Hye Youn Sung, Jihye Han, Woong Ju, Jihee Lee Kang, Ae Kyung Park, Jung-Hyuck Ahn
{"title":"MBNL2 enhances cisplatin resistance by regulating apoptosis in ovarian cancer cells.","authors":"Hye Youn Sung, Jihye Han, Woong Ju, Jihee Lee Kang, Ae Kyung Park, Jung-Hyuck Ahn","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Although cisplatin is an effective anticancer agent for treating ovarian cancer, it encounters significant resistance. A full understanding of the mechanisms behind cisplatin resistance has not been achieved. This study identifies MBNL2 as a crucial regulator of cellular responses to cisplatin, examining variations in gene expression and methylation profiles between cisplatinsensitive and -resistant ovarian cancer cells. Cells resistant to cisplatin exhibited increased MBNL2 mRNA expression and significant demethylation at promoter CpG sites. Treating ovarian cancer cell lines with a DNA demethylating agent significantly raised MBNL2 mRNA expression, indicating that epigenetic mechanisms involving DNA methylation control MBNL2 expression. Modulating MBNL2 levels altered the response to cisplatin through survival pathways that shield cells from cisplatin-induced apoptosis. Overexpressing MBNL2 enhanced resistance, while its depletion heightened cisplatin sensitivity. Furthermore, MBNL2 mRNA levels differed among patients based on their response to platinum-based chemotherapeutics. Patients resistant to these drugs had higher MBNL2 mRNA levels, effectively distinguishing them from those who were sensitive (AUC = 0.89, P = 0.0308). A meta-analysis of seventeen datasets confirmed that lower MBNL2 expression levels are associated with a better chemotherapy response and longer relapse-free survival. Conversely, higher MBNL2 expression levels correlated with increased recurrence rates and reduced survival. Thus, MBNL2 may serve as a promising prognostic and therapeutic target for overcoming cisplatin resistance. [BMB Reports 2025; 58(5): 224-231].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"224-231"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12123203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770966","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":"Role of Arabidopsis monomeric E3 ubiquitin ligases in the ABA signaling pathway.","authors":"Sunglan Chung, Su-Jung Lee, Hye Sup Yun, Jae-Hoon Lee, Woo Taek Kim","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Abscisic acid (ABA) is a key phytohormone that regulates multiple biological processes in plants, including seed germination, seedling growth, and abiotic stress response. ABA enhances drought tolerance by promoting stomatal closure, thereby improving crop productivity under unfavorable stress conditions. Extensive research efforts have focused on understanding ABA signaling more clearly for its potential application in agriculture. The accumulation and stability of signaling components involved in the efficient transduction of downstream ABA signaling are affected by both transcriptional regulation and post-translational modifications. Ubiquitination is a representative post-translational modification that regulates protein stability, and E3 ubiquitin ligase is a key enzyme that determines target substrates for ubiquitination. To date, many E3 ligases functioning as a monomeric form such as RING-, HECT- and Ubox- types have been known to participate in the ABA signaling process. In this review, we summarize the current understanding of ABA-related monomeric E3 ligases, their regulation, and mode of action in Arabidopsis, which will help develop a detailed and integrated understanding of the ABA signaling process in Arabidopsis. [BMB Reports 2025; 58(4): 147-157].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"147-157"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584425","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}
Eunbi Yoo, Yeleen Jo, Jooyoun Park, Sung-Wook Hong
{"title":"Immune tolerance to foreign antigens in the intestine: mechanisms mediated by CD4+ T cells.","authors":"Eunbi Yoo, Yeleen Jo, Jooyoun Park, Sung-Wook Hong","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The immune system encounters a diverse array of antigens, both self and foreign, necessitating mechanisms to maintain tolerance and prevent harmful inflammatory responses. CD4+ T cells, crucial in orchestrating immune responses, play a critical role in mediating tolerance to both self and foreign antigens. While the mechanisms of CD4+ T cell-mediated tolerance to self-antigens are well-documented, the understanding of tolerance to foreign antigens, including those from commensal microbes and food, remains incomplete. This review discusses recent progress in the mechanisms underlying immune tolerance to foreign antigens, with a focus on the role of CD4+ T cells. We explore how inflammatory and tolerogenic CD4+ T cell subsets are developed and maintained. Moreover, we delve into the complexities of immune responses to commensal microbes and food antigens by reviewing recent findings, highlighting the immunological contexts that shape immune tolerance. Understanding these mechanisms enhances our comprehension of how immune tolerance is established and sustained, providing insights into potential therapeutic approaches for managing chronic inflammatory diseases resulting from a loss of immune tolerance to foreign antigens. [BMB Reports 2025; 58(4): 158-168].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"158-168"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770948","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}
Jin Sun Choi, Ji-Young Kim, Min-Joo Ahn, Seungtaek Song, Doyoun Kim, Sung Hoon Choi, Ye-Soo Park, Tae-Jong Kim, Sungsin Jo, Tae-Hwan Kim, Seung Cheol Shim
{"title":"Erratum to: Celecoxib is the only nonsteroidal anti-inflammatory drug to inhibit bone progression in spondyloarthritis.","authors":"Jin Sun Choi, Ji-Young Kim, Min-Joo Ahn, Seungtaek Song, Doyoun Kim, Sung Hoon Choi, Ye-Soo Park, Tae-Jong Kim, Sungsin Jo, Tae-Hwan Kim, Seung Cheol Shim","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>[Erratum to: BMB Reports 2025; 58(3): 140-145, PMID: 39757202, PMCID: PMC11955732] The BMB Reports would like to issue a correction to an article published in BMB Rep. 58(3): 140-145, titled \"Celecoxib is the only nonsteroidal anti-inflammatory drug to inhibit bone progression in spondyloarthritis\". The original acknowledgment contained incorrect grant information. This has now been corrected at the authors' request as follows: This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2016R1 A6A3A11930589, NRF-2016R1A6A3A11934500, NRF-2016 R1D1A3 B03931646, NRF-2019R1I1A1A01057738, NRF-2019R1l1A3A01060016, NRF-2019R1l1A1A01060116, and RS-2023-00248058). It was also supported by the Chungnam National University Hospital Research Fund 2021 (2021-CF-033). Specifically, the grant number has been updated from 2016 (2016-CF-003) to 2021 (2021-CF-033). 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.</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":"58 4","pages":"190"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959470","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}