BMB Reports最新文献

Immune tolerance to foreign antigens in the intestine: mechanisms mediated by CD4＋ T cells.

IF 2.9 3区生物学

BMB Reports Pub Date : 2025-04-03

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":"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.","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

VCAM1-mediated regulation of dopaminergic neuron function in Parkinson's disease.

IF 2.9 3区生物学

BMB Reports Pub Date : 2025-04-03

Mihee Oh, Sunha Lee, Eunhye Kim, Yewon Jang, Baek-Soo Han

引用次数: 0

Tissue-specific lncRNA GATA6-AS1 and its ortholog Moshe as essential regulators of aortic valve development.

IF 2.9 3区生物学

BMB Reports Pub Date : 2025-04-03

Na-Jung Kim, Eun-Hye Moon, Ji Hoon Oh, Hyeon Myeong Kim, Su Haeng Sung, Han-Se Kim, Chae-Yi Kim, Yeo-Jin Im, Jasmin E Turner, Young Jae Lee, Yong Jun Kim, Je-Yoel Cho

{"title":"Tissue-specific lncRNA GATA6-AS1 and its ortholog Moshe as essential regulators of aortic valve development.","authors":"Na-Jung Kim, Eun-Hye Moon, Ji Hoon Oh, Hyeon Myeong Kim, Su Haeng Sung, Han-Se Kim, Chae-Yi Kim, Yeo-Jin Im, Jasmin E Turner, Young Jae Lee, Yong Jun Kim, Je-Yoel Cho","doi":"","DOIUrl":"","url":null,"abstract":"Long noncoding RNAs (lncRNAs) are integral to epigenetic regulation during cardiogenesis; however, their role in aortic valve disease is not well characterized. Investigating lncRNAs present in the human embryonic heart and pinpointing their specific isoforms presents notable challenges due to both technical and ethical limitations. In our research, we identified GATA6-AS1 as a lncRNA predominantly found in the heart by analyzing publicly accessible RNA sequencing data derived from human embryonic tissues. Employing in vitro models along with CS17 embryonic heart tissue, we determined that isoforms 202 and 208 of GATA6-AS1 are uniquely expressed in cardiac neural crest lineage cells throughout the development of the aortic valve. We also identified Moshe, the murine ortholog of GATA6-AS1, whose expression occurs during aortic valve formation in mice. Notably, depletion of Moshe results in the development of bicuspid aortic valves (BAV), accompanied by a significant downregulation of genes associated with BAV, particularly those related to the Notch and TGF-β signaling pathways. These findings highlight the critical role of GATA6-AS1 in aortic valve development through the study of its mouse ortholog Moshe. They also suggest that lncRNAs, still underexplored in congenital heart disease research, may hold significant implications for BAV pathogenesis and potential therapeutic strategies.","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770925","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}

引用次数: 0

MBNL2 enhances cisplatin resistance by regulating apoptosis in ovarian cancer cells.

IF 2.9 3区生物学

BMB Reports Pub Date : 2025-04-03

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":"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.","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Potential use of human pluripotency-related gene expression reporter cell line for screening small molecules to enhance induction of pluripotency.

IF 2.9 3区生物学

BMB Reports Pub Date : 2025-04-03

Seokbeom Ham, Minseong Lee, Dahee Jeong, Jaeseung Son, Yerin Kim, Taebok Lee, Kisung Ko, Sang Hyun Moh, Kinarm Ko

{"title":"Potential use of human pluripotency-related gene expression reporter cell line for screening small molecules to enhance induction of pluripotency.","authors":"Seokbeom Ham, Minseong Lee, Dahee Jeong, Jaeseung Son, Yerin Kim, Taebok Lee, Kisung Ko, Sang Hyun Moh, Kinarm Ko","doi":"","DOIUrl":"","url":null,"abstract":"The reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) is a crucial development in regenerative medicine, providing patient-specific cells for therapeutic uses. Traditional methods often utilize viral vectors and transcription factors that pose tumorigenic risks, rendering them unsuitable for clinical applications. This study explored the use of chemicals as a non-tumorigenic alternative for cell reprogramming. Utilizing CRISPR/Cas9 technology, we previously created iPSCs expressing OCT4-EGFP and NANOG-tdTomato, and derived OCT4-EGFP and NANOG-tdTomato fibroblastic cells (ON-FCs). These cells were reprogrammed using episomal vectors, and their pluripotency was validated by fluorescence and FACS analyses. High-content screening was employed to assess small molecules that improve reprogramming efficiency, confirming the usefulness of ON-FCs as a dual reporter cell line for identifying small molecules effective in generating human iPSCs. This study underscores the utility of a dual reporter system and high-content screening in identifying effective reprogramming chemicals, establishing a scalable platform for high-throughput screening. Discovering new chemicals that can reprogram iPSCs would provide a non-tumorigenic method to advance the field of regenerative medicine.","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770975","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}

引用次数: 0

Role of Arabidopsis monomeric E3 ubiquitin ligases in the ABA signaling pathway.

IF 2.9 3区生物学

BMB Reports Pub Date : 2025-03-05

Sunglan Chung, Su-Jung Lee, Hye Sup Yun, Jae-Hoon Lee, Woo Taek Kim

{"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":"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.","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unraveling the three-dimensional genome structure using machine learning.

IF 2.9 3区生物学

BMB Reports Pub Date : 2025-03-05

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":"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.","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deubiquitinase dynamics: methodologies for understanding substrate interactions.

IF 2.9 3区生物学

BMB Reports Pub Date : 2025-03-05

Sang-Ah Park, Ji Min Lee

{"title":"Deubiquitinase dynamics: methodologies for understanding substrate interactions.","authors":"Sang-Ah Park, Ji Min Lee","doi":"","DOIUrl":"","url":null,"abstract":"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.","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Celecoxib is the only nonsteroidal anti-inflammatory drug to inhibit bone progression in spondyloarthritis. 塞来昔布是唯一的非甾体抗炎药，以抑制脊柱关节炎的骨骼进展。

IF 2.9 3区生物学

BMB Reports Pub Date : 2025-03-01

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":"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":"Spondyloarthritis (SpA) is a chronic inflammatory disease that leads to ankylosis of the axial skeleton. Celecoxib (cyclooxygenase-2 inhibitor, COX-2i) inhibited radiographic progression in a clinical study of SpA, but in the following study, diclofenac (COX-2 non-selective) failed to show that inhibition. Our study aimed to investigate whether nonsteroidal anti-inflammatory drugs (NSAIDs) inhibited bone progression in SpA, and whether celecoxib had a unique function (independent of the COX-inhibitor), compared with the other NSAIDs. We investigated the efficacy of various NSAIDs in curdlan-injected SKG mice (SKGc), an animal model of SpA, analyzed by bone micro-CT and immunohistochemistry. We also tested the effect of NSAIDs on osteoblast (OB) differentiation and bone mineralization in primary bone-derived cells (BdCs) from mice, and in ankylosing spondylitis (AS) patients and human osteosarcoma cell line (SaOS2). Celecoxib significantly inhibited clinical arthritis and bone progression in the joints of SKGc, but not etoricoxib (another COX-2i), nor naproxen (COX-2 nonselective). Both DM-celecoxib, not inhibiting COX-2, and celecoxib, inhibited OB differentiation and bone mineralization in the BdCs of mice and AS patients, and in SaOS2, but etoricoxib or naproxen did not. The in silico study indicated that celecoxib and 2,5-dimethyl-celecoxib (DM-celecoxib) would bind to cadherin-11 (CDH11) with higher affinity than etoricoxib and naproxen. Celecoxib suppressed CDH11-mediated β-catenin signaling in the joints of SKGc, primary mice cells, and SaOS2 cells. Of the NSAIDs, only celecoxib inhibited bone progression in SKGc and OB differentiation and bone mineralization in the BdCs of mice and AS patients via CDH11/WNT signaling, independent of the COX-2 inhibition. [BMB Reports 2025; 58(3): 140-145].","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"140-145"},"PeriodicalIF":2.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930671","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}

引用次数: 0

Diverse nanoparticles deliver mRNA to enhance tumor immunotherapy.

IF 2.9 3区生物学

BMB Reports Pub Date : 2025-03-01

Wei He, Meng Zhang, Yuexia Zhong, Yuan Gao, Dong Fan, Xiyan Lu

{"title":"Diverse nanoparticles deliver mRNA to enhance tumor immunotherapy.","authors":"Wei He, Meng Zhang, Yuexia Zhong, Yuan Gao, Dong Fan, Xiyan Lu","doi":"","DOIUrl":"","url":null,"abstract":"Limited efficacy and severe side effects often result in suboptimal outcomes to solid tumor therapies. In contrast, the reduced side effects and potential long-term benefits of tumor immunotherapy offer promise, notwithstanding the challenges of variable patient responses and immune-related adverse events hindering its widespread application. Recent advances in mRNA technology have revolutionized cancer immunotherapy. The versatility of mRNA as a vaccine and therapeutic agent is evident in it overcoming the limitations of traditional approaches by reducing in vivo toxicity and enhancing immune response activation. The synergy between mRNA technology and immunotherapy is increasingly being utilized to improve cancer treatment efficacy. One critical aspect of maximizing the therapeutic impact of mRNA-based treatments is the selection of an effective delivery system. Due to their size properties and material characteristics, nanoparticles offer a transformative solution, enabling the targeted and efficient delivery of mRNA to tumor tissues or immune cells. This precision delivery mechanism significantly enhances the effectiveness of immunotherapy, and represents a significant advance in cancer treatment. This review aims to explore how mRNA delivery via nanoparticles enhances tumor immunotherapy. Examination of its applications and challenges provides insights and strategic perspectives to advance this innovative therapeutic approach. [BMB Reports 2025; 58(3): 124-132].","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"124-132"},"PeriodicalIF":2.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584423","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}

引用次数: 0