Ju Won Kim, Sanghyun Lee, Sejin Jeon, Sun-Woo Yoon, Yo Han Jang
{"title":"Stigmasterol elicits antiviral activity against influenza viruses through virucidal and entry inhibition activity in vitro","authors":"Ju Won Kim, Sanghyun Lee, Sejin Jeon, Sun-Woo Yoon, Yo Han Jang","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Influenza viruses pose a significant global public health threat, leading to recurrent seasonal epidemics and occasional pandemics. The rising prevalence of drug-resistant strains highlights the urgent need for new antiviral agents with alternative mechanisms of action. Plant-derived natural products have emerged as promising antiviral resources due to their chemical diversity and wide range of biological activities. Stigmasterol, a naturally occurring phytosterol found in various plants, is recognized for its anti-inflammatory and antioxidant properties; however, its antiviral potential against influenza viruses has not been clearly established. In this study, we systematically assessed the antiviral activity of stigmasterol against influenza A and B viruses in vitro. Stigmasterol demonstrated significant virucidal activity against both virus types at non-cytotoxic concentrations and effectively interfered with the functions of the viral surface proteins hemagglutinin and neuraminidase. Using GFP-expressing reporter viruses and cytopathic effect reduction assays, we showed that stigmasterol robustly suppressed viral infection under pre-, co-, and post-treatment conditions. Importantly, stigmasterol inhibited viral entry through a mechanism independent of hemagglutinin inhibition. These findings provide the first evidence that stigmasterol has broad anti-influenza activity and support its potential as a plant-derived lead compound for developing novel therapeutic strategies against influenza infection.</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697520","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":"Enzyme-assisted extraction of plant-derived extracellular vesicles: recent advances, methodological considerations, and standardization needs.","authors":"Hyun Chul Jo, Seongje Hong, Kyung Oh Jung","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Plant-derived extracellular vesicles (PDEVs) have attracted increasing attention as bioactive nanostructures with emerging applications in medicine, functional foods, and cosmetics. However, unlike mammalian extracellular vesicle systems, the recovery of PDEVs is fundamentally constrained by plant-specific structural features, particularly the rigid cell wall and the limited accessibility of vesicles within plant tissues. In plant systems, extracellular vesicles are thought to be retained, at least in part, within the apoplastic space between the plasma membrane and the cell wall, which restricts the direct application of conventional animal cell-based isolation workflows. Conventional extraction approaches based on mechanical disruption enable bulk recovery of vesicle-containing material but are frequently associated with intracellular contamination, cell wall-derived debris, increased extract viscosity, and poor process reproducibility. To address these limitations, recent studies have explored enzyme-based extraction strategies that partially relax the plant cell wall to facilitate the selective release of apoplastic vesicles while reducing nonspecific contamination. In this mini-review, we summarize recent advances in enzyme-based extraction strategies for PDEVs, with particular emphasis on their structural rationale, methodological advantages over mechanical disruption, and associated limitations. We further discuss key challenges in quantitative evaluation, purity assessment, and reporting standardization, highlighting the need for methodologically rigorous frameworks to enable reproducible isolation and reliable interpretation of PDEV-associated biological activities.</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147621812","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}
Se Rok Jeong, Yong Taek Jeong, Chul Hoon Kim, Jeong Taeg Seo, Seok Jun Moon
{"title":"Loss of Tubby in MC4R- and VGLUT2-Expressing Neurons Impairs Energy Homeostasis.","authors":"Se Rok Jeong, Yong Taek Jeong, Chul Hoon Kim, Jeong Taeg Seo, Seok Jun Moon","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Obesity is a major global health crisis, yet the molecular mechanisms underlying adult-onset metabolic dysfunction remain incompletely understood. The tubby mouse is a foundational genetic model of maturity-onset obesity; however, the specific tissues and cell populations responsible for its metabolic phenotype have long remained elusive. Here, we demonstrate that the loss of tubby disrupts the coordinated regulation of energy intake and expenditure, leading to a sustained positive energy balance. Using cell-type-specific genetic tools, we identified MC4R-expressing and VGLUT2-expressing neurons as essential sites of tubby function. We found that tubby acts through the combined contribution of these neuronal populations, as selective deletion in either MC4R or VGLUT2 neurons is sufficient to phenocopy key features of the global Tub mutant. Together, these findings establish tubby as a central neuronal regulator of systemic energy homeostasis and define an excitatory MC4R-VGLUT2 circuit that governs feeding behavior and metabolic output.</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147621414","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}
Seungwon An, Chung Hyo Kang, Taehyun Park, Balachandar Nedumaran, Younjoo Sung, Taehoon Chung, Chul-Seung Park, Ali R Djalilian, Yong Deuk Kim
{"title":"Cereblon enhances hepatic hepcidin production through estrogen-related receptor gamma activation.","authors":"Seungwon An, Chung Hyo Kang, Taehyun Park, Balachandar Nedumaran, Younjoo Sung, Taehoon Chung, Chul-Seung Park, Ali R Djalilian, Yong Deuk Kim","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Hepcidin (encoded by the HAMP gene), produced primarily by hepatocytes, is the master regulator of systemic iron homeostasis, and its dysregulation contributes to various iron-related metabolic disorders. Cereblon (CRBN) has been implicated in metabolic regulation, while estrogen-related receptor gamma (ESRRG) is known to govern energy homeostasis and mitochondrial function. Here, we demonstrate a novel CRBN-ESRRG signaling pathway that mediates endoplasmic reticulum (ER) stress-induced hepatic HAMP expression. In mice and primary hepatocytes exposed to tunicamycin-induced ER stress, gene expression and biochemical analyses revealed that hepatic Crbn, Esrrg, and Hamp transcript levels were significantly increased. Hepcidin protein levels were correspondingly elevated, accompanied by reduced serum iron levels and increased cellular iron levels, consistent with hepcidin-mediated regulation of iron distribution. Overexpression of Crbn enhanced ESRRG expression and increased hepatic hepcidin production, whereas Crbn or Esrrg knockdown attenuated this response. Chromatin immunoprecipitation assays demonstrated enhanced ESRRG recruitment to the Hamp promoter. Collectively, these findings identify a CRBN-ESRRG regulatory axis that drives hepatic HAMP expression under ER stress and suggest a potential therapeutic target for ER stress-associated metabolic and iron disorders.</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147621803","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}
Dohee Kim, Seo-Eun Lee, JuHyuen Cha, Jun Ho Lee, Young Cheol Kang, Sang-Yeon Lee
{"title":"Mitochondrial transplantation restores mitochondrial content and function in SSBP1-related mitochondrial DNA depletion syndrome.","authors":"Dohee Kim, Seo-Eun Lee, JuHyuen Cha, Jun Ho Lee, Young Cheol Kang, Sang-Yeon Lee","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>This study examined therapeutic potential of mitochondrial transplantation using PN-101, a mitochondria preparation derived from human umbilical cord mesenchymal stem cells (UCMSCs), to address SSBP1-related mitochondrial DNA (mtDNA) depletion syndrome. Patient-derived fibroblasts harboring a heterozygous SSBP1 mutation (c.272G>A:p.Arg91Gln) were treated with PN-101. Its successful uptake and integration into these cells were confirmed. Subsequent analyses revealed that PN-101 treatment significantly increased mtDNA copy numbers in a time- and dose-dependent manner, elevated the expression of key oxidative phosphorylation proteins, and enhanced overall mitochondrial bioenergetics. Taken together, these results provide strong evidence that mitochondrial transplantation holds promise as a therapeutic strategy for primary mitochondrial diseases, including those involving SSBP1 mutations. [BMB Reports 2026; 59(4): 227-234].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"227-234"},"PeriodicalIF":3.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145556300","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}
Yoonji Oh, Hanbyeol Kim, Sanghyun Lee, Soon-Jung Park, Yun-Gwi Park, Sung-Hwan Moon, Inkyung Jung, Chul-Hwan Lee
{"title":"Comparative analyses of ChIP-seq, CUT&RUN and CUT&Tag for Polycomb chromatin profiling.","authors":"Yoonji Oh, Hanbyeol Kim, Sanghyun Lee, Soon-Jung Park, Yun-Gwi Park, Sung-Hwan Moon, Inkyung Jung, Chul-Hwan Lee","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Chromatin profiling methods such as ChIP-seq, CUT&RUN, and CUT&Tag differ substantially in background structure, signal distribution, and resolution, complicating direct quantitative comparison across platforms. In this study, we systematically compared conventional and double-crosslink ChIP-seq, CUT&RUN, and CUT&Tag by profiling the Polycomb-associated histone modification H3K27me3 in human cardiomyocytes and the PRC2 catalytic subunit EZH2 in pluripotent stem cells. To enable cross-assay comparison, we developed a biologically informed normalization strategy based on stable Polycomb reference loci, allowing harmonization of signal scales while preserving assay-intrinsic signal architecture. This approach revealed CUT&RUN to preferentially capture broad H3K27me3 domains, whereas CUT&Tag provides sharper and more localized enrichment for both H3K27me3 and EZH2. Together, our results establish a practical framework for cross-platform epigenomic comparison and guide the selection of chromatin profiling strategies. [BMB Reports 2026; 59(4): 242-252].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"242-252"},"PeriodicalIF":3.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147353619","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":"New approach methodologies to model liver fibrosis in metabolic dysfunction-associated steatohepatitis.","authors":"Seung Min Lee, Da Kyung Hwang, Hyun Young Kim","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatohepatitis (MASH) is a significant global health issue and a leading cause of liver fibrosis, with no effective pharmacological treatments available. Conventional 2D cell cultures and animal models do not fully recapitulate the complex cell-cell interactions and multicellular microenvironment that drive disease progression in humans, which limits their ability to predict therapeutic efficacy accurately. The recent introduction of the FDA Modernization Act 2.0 has paved the way for the use of human-relevant New Approach Methodologies (NAMs) in drug discovery and toxicity testing. This review focuses on recent advancements in NAMs that model MASH-associated liver fibrosis, such as human liver spheroids, iPSC-derived liver organoids, precision-cut liver slices, 3D bioprinting, and liver-on-a-chip systems. By mimicking multicellular interactions and the liver microenvironment, NAMs offer a valuable platform for mechanistic studies and drug screening. Assessing their strengths and limitations can lead to deeper mechanistic insights and expedite the development of new therapeutics for MASH-associated liver fibrosis. [BMB Reports 2026; 59(4): 219-226].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"219-226"},"PeriodicalIF":3.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147688075","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":"Reverse beta-oxidation for biochemical production: insights into the functional properties of key enzymes.","authors":"Areum Lee, Hyeoncheol Francis Son","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The reverse β-oxidation (rBOX) pathway is emerging as a promising alternative to fossil fuel-based chemical production, providing a versatile platform for the synthesis of various valueadded biochemicals. Efficient application of rBOX depends on the selection of enzymes with high catalytic activity, suitable substrate specificity, and strong functional compatibility within the pathway. In this review, we focus on the structural and biochemical characteristics of four key enzymes-thiolase, 3-hydroxyacyl-CoA dehydrogenase, enoyl-CoA hydratase, and enoyl-CoA reductase-and explore how their individual features and combinations influence pathway performance. We then summarize previous studies that highlight the importance of enzyme cooperation in achieving optimal production outcomes. These insights provide valuable guidance for the rational design of rBOX-based biosynthetic pathways tailored to specific chemical targets. [BMB Reports 2026; 59(4): 209-218].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"209-218"},"PeriodicalIF":3.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145013836","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}
Jung Ha Kim, Kabsun Kim, Inyoung Kim, Semun Seong, Wonbong Lim, Jeong-Tae Koh, Nacksung Kim
{"title":"CaMKIV negatively regulates osteoblast differentiation by modulating c-Fos and NFATc1 signaling: an in vitro and in vivo mechanistic study.","authors":"Jung Ha Kim, Kabsun Kim, Inyoung Kim, Semun Seong, Wonbong Lim, Jeong-Tae Koh, Nacksung Kim","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The CaMKIV-c-Fos-NFATc1 axis is established in osteoclastogenesis, but its role in osteoblasts is largely unexplored. We show that this axis suppresses osteoblast differentiation and bone formation. Silencing CaMKIV increased osteogenic gene expression and mineralization, whereas overexpressing c-Fos or NFATc1 reduced osteoblast activity. Mechanistically, CaMKIV binds c-Fos and inhibits its ubiquitination, stabilizing c-Fos and elevating NFATc1. NFATc1, in turn, impairs Runx2 acetylation by competing for PCAF, thereby attenuating osteoblast maturation. Pharmacological CaMKIV inhibition with STO-609 increased bone formation in vitro and enhanced ectopic bone formation in vivo, supporting CaMKIV as a potential anabolic target for bone regeneration. [BMB Reports 2026; 59(4): 235-241].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"235-241"},"PeriodicalIF":3.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146141337","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}
Hyang Sook Seol, Jaewon Kim, Ju Hee Oh, Eunhye Choi, Sanghyuk Lee, Eun Ji Nam, Jaesang Kim
{"title":"PPP1R3C functions as a tumor suppressor in endometrial cancer through promotion of glycogen synthesis.","authors":"Hyang Sook Seol, Jaewon Kim, Ju Hee Oh, Eunhye Choi, Sanghyuk Lee, Eun Ji Nam, Jaesang Kim","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In this study, we report a novel function of protein phosphatase 1 regulatory subunit 3C (PPP1R3C)-which is known to promote glycogenesis by activating glycogen synthase and to inhibit glycogen breakdown by suppressing glycogen phosphorylase- as a tumor suppressor in endometrial cancer. First, the expression of PPP1R3C was strongly down-regulated in uterine corpus endometrial cancer (UCEC) tissues, and ectopic expression of PPP1R3C led to cell cycle arrest and apoptosis in HEC1A and HEC1B cells derived from UCEC. PPP1R3C also inhibited the growth of xenograft tumors in BALB/c nude mice. We found evidence indicating that the activation of glycogen synthesis was at least partly responsible for the tumor suppressor activity of PPP1R3C. Specifically, inhibition of glycogen synthase abrogated the effect of ectopic PPP1R3C expression on the growth inhibition of UCEC cells. Collectively, our data indicate that PPP1R3C is a tumor suppressor gene functioning through the induction of glycogen synthesis.</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147353778","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}