Radial glia are the principal neural stem cells in the developing human cerebral cortex and have been classified as three molecularly distinct subtypes: ventricular radial glia (vRG), outer radial glia (oRG), and truncated radial glia (tRG). Human cortical organoids (hCOs) from human pluripotent stem cells that recapitulate the developmental program of human cortex have shown this progenitor diversity. vRG and oRG are readily generated and identified in hCOs from most differentiation protocols with oRG emergence dependent on specific signaling pathway, such as LIF/STAT3 supplementation. However, tRGs that have only recently been defined at the molecular level have not been systematically examined in any organoid system. Here we review the biology, signaling, and lineage potential of each radial glial subtype and assess how faithfully they are represented in cortical organoids. We highlight and discuss the studies on the tRG from hCOs. We discuss data that support the presence of tRG in hCOs, including ependymal cell generation from radial glia within organoids, CRYAB-positive progenitors in three-dimensional culture systems, and tRG-associated transcriptomic change upon genetic perturbation. However, definitive identification through combinatorial marker co-expression and morphological validation has not yet been achieved. Faithfully establishing molecular signatures and signaling frameworks for tRG and their existence in hCOs will provide the foundation for systemically investigating the development and function of this cell type in vitro. We discuss future directions for resolving whether tRG is generated during the neurogenesis-to-gliogenesis transition.

Epigallocatechin gallate (EGCG), a major polyphenol in green tea, exhibits anti-obesity effects, but its precise mechanism remains to be fully elucidated. In this study, we found that EGCG suppresses the adipocyte differentiation of 3T3-L1 cells, which was achieved with its treatment limited to the first two days post-differentiation induction. EGCG inhibited the tetranectin (TN)-mediated increase in ERK and AKT phosphorylation. EGCG efficiently removed TN in the differentiation medium, suggesting TN as a direct target. Furthermore, TN was found to undergo endocytosis during early differentiation, which was attenuated by EGCG, indicating a potential intracellular role for TN. Collectively, these findings demonstrate that EGCG suppresses adipogenesis by reducing TN availability in the medium and inhibiting its subsequent endocytosis, thereby modulating the ERK and AKT signaling pathways.

Alzheimer's disease (AD) is marked by progressive cognitive decline and retinal abnormalities, including degeneration of the retinal pigment epithelium (RPE). In models of AD, the accumulation of amyloid-β (Aβ) peptides triggers chronic inflammation and activates the immunoproteasome (iP), primarily driven by tumor necrosis factor-alpha (TNFα) from glial cells. Although pharmacological inhibition of iP has demonstrated protective effects against retinal damage, the precise molecular mechanisms involved remain unclear. In this study, we reveal that Aβ stimulation initiates a signaling cascade from glia to RPE, mediated by TNFα, which in turn promotes iP activation and upregulation of the NLRP3 inflammasome in RPE cells. Aβ exposure significantly increased TNFα secretion in Müller glia, whereas RPE cells exhibited only a minimal intrinsic response to TNFα secretion in response to Aβ. Inhibition of iP reduced TNFα release from glial cells. Additionally, neutralizing gliaderived TNFα decreased iP activity and mitigated epithelialmesenchymal transition (EMT) in RPE cells, highlighting TNFα's crucial role in glial-induced retinal inflammation. These findings position glia-derived TNFα as a central factor in Aβ-induced RPE degeneration through the TNFα-iP-NLRP3 pathway, supporting the use of iP inhibition as a potential therapeutic approach to maintain retinal integrity in AD.

Hair loss is a psychologically debilitating condition affecting social interactions. Despite extensive research, current interventions are transient and provide limited efficacy. Emerging evidence highlights that oxidative stress, resulting from mitochondrial dysfunction, impairs hair growth and disrupts hair cycle regulation. Urolithin A (UA), known to enhance mitochondrial function via mitophagy activation, has not yet been studied for its protective effects against hair loss. Here, we investigate whether UA protects against oxidative stress and promotes hair growth by restoring mitochondrial function in human dermal papilla cells (hDPCs) and clinical cases. hDPCs were subjected to H2O2 to induce oxidative stress and treated with various UA concentrations. Protective effects were assessed via mitochondrial function, morphology, apoptosis assays and Wnt/β-catenin signaling activity. Clinical evaluation involved measuring hair root volume and shedding rates following topical UA application. UA treatment improved mitochondrial function, reduced cell death under oxidative stress conditions, and activated Wnt/β-catenin signaling by increasing Wnt and β-catenin expression in hDPCs. Clinically, UA application led to increased hair root volume and decreased hair shedding. These dual effects on mitochondrial function and Wnt/β-catenin signaling highlight the potential of UA as a novel intervention for hair loss management.

The specific roles of single-nucleotide polymorphisms and structural variants (SVs) in Korean patients with inflammatory bowel disease (IBD) susceptibility remain unclear; hence this study aimed to evaluate polygenic risk scores (PRS) for IBD and identify IBD-associated SVs in a Korean IBD cohort. Whole genome sequencing data from 75 Korean patients with IBD were analyzed, and compared with individuals from the general Korean population cohort. The PRS models significantly distinguished patients with IBD from the general Korean population, confirming the predictive power of PRS in Korean patients with IBD. SV analysis revealed IBD-associated deletions, with candidate loci including PLA2R1, PTPN2, LINC00484, CCND3, COMMD7, and ERAP2. Of these, DEL5948 in ERAP2 overlapped multiple IBD-associated SNP loci and disrupted key regulatory and coding regions, potentially influencing immune regulation. This study provides a comprehensive genome-wide analysis of PRS and SVs in Korean patients with IBD, highlighting novel genetic factors in IBD pathogenesis.

Targeting the behavior of myeloid-derived suppressor cells (MDSCs), either by decreasing their population or inhibiting their immunosuppressive activity, has become a promising approach in breast cancer therapy. As pivotal mediators within the tumor microenvironment (TME), MDSCs facilitate tumor progression via diverse mechanisms, including T-cell suppression, epithelial-mesenchymal transition (EMT), and the preservation of cancer cell stemness. EK-16005, a novel 2-anilinopyrimidine derivative, has shown robust inhibitory activity against breast cancer cells. In this investigation, we examined the impact of EK-16005 on the reciprocal interactions between MDSCs and cancer cells that modulate cytokine production and signaling pathway activation. EK-16005 downregulated the secretion of critical cytokines such as G-CSF, VEGF, and CXCL1/2, leading to blockade of STAT3 and Notch signaling cascades in vitro and in vivo. As a result, EK-16005 decreased MDSC expansion, tumor growth, and cancer stemness properties. Collectively, these results establish EK-16005 as a potential therapeutic candidate for interrupting MDSC-mediated tumor progression and improving outcomes in breast cancer treatment.

Colorectal cancer (CRC) poses major clinical challenges, and deeper molecular and immunological insights are essential for precision oncology. We integrated RNA sequencing (RNA-seq) and clinical data from a Korean CRC cohort to profile tumor biology and immune heterogeneity. Differential expression analysis revealed 1,652 upregulated and 1,372 downregulated genes in tumors, with enrichment of DNA damage response (DDR), WNT signaling, and extracellular matrix (ECM)- receptor pathways, whereas normal tissues were enriched for metabolic processes. Consensus Molecular Subtype (CMS) classification identified canonical subtype-specific features, with unclassified tumors resembling CMS2. Immune phenotyping stratified tumors into hot, intermediate, and cold groups, showing distinct associations with microsatellite instability (MSI) and CMS subtypes. Tumor Immune Dysfunction and Exclusion (TIDE) analysis predicted responders across all phenotypes, unexpectedly including intermediate and cold tumors. Notably, interferon-STAT3-PIM1 signaling characterized non-responders, implicating oncogenic drivers of immune resistance. Immunehot tumors displayed strong antigen presentation (HLA-C, B2M) and apoptosis (FAS) signatures, supporting sensitivity to PD-1 blockade with potential benefit from apoptosis-targeting agents. Intermediate tumors showed partial CD8＋ T cell activation, suggesting combinatorial strategies such as CTLA-4 blockade or oncolytic priming. Cold tumors with IRF1 expression exhibited latent immune potential, indicating opportunities for epigenetic modulation plus checkpoint inhibition. These findings highlight the immune transcriptomic diversity of CRC and demonstrate that immune phenotype-based stratification provides actionable insights beyond MSI or CMS classification. This framework may guide personalized immunotherapy strategies for Korean CRC patients and inform future integration with spatial transcriptomic profiling.

Prime editing is a next-generation genome editing technology that enables precise base substitutions, insertions, and deletions at target genomic loci without inducing double-strand breaks or requiring exogenous donor DNA. This system operates through a fusion protein composed of Cas9 nickase and reverse transcriptase together with prime editing guide RNA; it has emerged as a precise genome editing platform that overcomes the limitations of conventional double-strand break-inducing CRISPR-Cas9 systems. Since first reported in 2019, diverse methodological improvements from PE1 to PE7 have been achieved, leading to rapid advances in editing efficiency, expansion of the editable target range, correction of large genomic regions, and development of in vivo delivery technologies. In this review, we comprehensively discuss the fundamental working mechanism of prime editing, its methodological evolution, recent expansion strategies, and delivery platforms for therapeutic applications, and provide perspectives for future development. [BMB Reports 2026; 59(6): 313-320].

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.

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].

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.

Hepcidin (encoded by the HAMP gene), produced primarily by hepatocytes, is the master regulator of systemic iron homeostasis. 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. In this study, 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 tunicamycininduced ER stress, gene expression and biochemical analyses revealed significant increases in the transcript levels of hepatic Crbn, Esrrg, and Hamp. Correspondingly, hepcidin protein levels were elevated, accompanied by reduced serum iron levels and increased cellular iron levels, consistent with hepcidinmediated regulation of iron distribution. Overexpression of Crbn enhanced ESRRG expression and increased hepatic hepcidin production, while knockdown of either Crbn or Esrrg attenuated this response. Chromatin immunoprecipitation assays demonstrated enhanced recruitment of ESRRG 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. [BMB Reports 2026; 59(5): 291-298].

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. [BMB Reports 2026; 59(5): 293-290].

Cellular senescence is an irreversible program of cell-cycle arrest that accumulates with age, contributing to chronic inflammation and various age-related diseases. A key feature of senescence paradigms is mitochondrial dysfunction, which involves not just a single defect but a series of coordinated changes in bioenergetics, redox homeostasis, mitochondrial quality control, and organelle interaction. Senescent cells often display a "quantity-quality imbalance" in their mitochondria: while the mitochondrial mass may increase, their efficiency in oxidative phosphorylation decreases, leading to a destabilized membrane potential (ΔΨm) and elevated levels of mitochondrial reactive oxygen species (mtROS). These interrelated changes can exacerbate senescence through persistent stress signaling, impaired turnover of damaged mitochondrial components, and alterations in organelle contacts, such as those between endoplasmic reticulum (ER) and mitochondria, and between mitochondria and lysosomes. Given that these phenotypes differ depending on cell type, triggering factors, and timing, no single assay can adequately define senescenceassociated mitochondrial dysfunction. In this review, we present practical, complementary strategies that include extracellular flux-based respiration profiling, ATP output measurement, ΔΨm and ROS assessments, flux-based mitophagy reporters, quantitative network imaging, and contact-site assays. We propose minimal assay bundles that allow for a thorough multidimensional analysis. By establishing standardized, orthogonal measures of mitochondrial quantity and quality, we aim to enhance mechanistic understanding and facilitate the rational evaluation of mitochondria-targeted senolytic and senomorphic therapies. [BMB Reports 2026; 59(3): 177-186].

Reactive Oxygen Species (ROS) accumulation disrupts cellular homeostasis, leading to lipid peroxidation, mitochondrial dysfunction, DNA damage, and apoptosis. Sestrin2 (Sesn2) is a critical antioxidant protein that regulates intracellular oxidative stress and protects cells from oxidative damage and apoptosis. However, the role of Sesn2 in ovarian reproductive function remains unclear. In this study, we examined Sesn2 expression in response to oxidative stress using granulosa-like KGN cells derived from human ovarian granulosa cell tumors, mouse granulosa cells, and an oxidative stress mouse model. Additionally, we investigated the protective Sesn2 functions and its mechanisms of action in promoting granulosa cell survival. The results showed that Sesn2 expression markedly increased in granulosa cells exposed to hydrogen peroxide (H2O2) and in oxidative stress models induced by 3-nitropropionic acid (3-NP). Oxidative stress in ovarian granulosa cells increases ROS levels, decreases cell viability, and triggers apoptosis. Sesn2 silencing further aggravates granulosa cell damage, whereas targeting Sesn2 under oxidative stress conditions reduces ROS levels and modulates apoptosis through the p53/Caspase-3 signaling pathway. These findings highlight the pivotal role of Sesn2 in protecting cells against ROS-induced damage, preserving follicular health, and supporting ovarian function and reproductive capacity.