International Journal of Molecular Sciences最新文献

{"title":"Expansion of the Phenotypic Spectrum of MNGIE: Lipodystrophy and Metabolic Alterations Associated with a p.Arg393_Val400dup TYMP Variant.","authors":"Donatella Gilio, Caterina Pelosini, Silvia Magno, Jacopo Maria Venanzi, Marta Daniotti, Melania Paoli, Lavinia Palladino, Maria Rita Sessa, Franco Ricci, Elena Procopio, Giovanni Ceccarini, Ferruccio Santini","doi":"10.3390/ijms26199751","DOIUrl":"10.3390/ijms26199751","url":null,"abstract":"<p><p>Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disorder caused by mutations in the <i>TYMP</i> gene, typically characterized by severe and progressive gastrointestinal and neurological manifestations. Recent reports have identified a subset of patients presenting with generalized lipodystrophy and metabolic abnormalities, suggesting that adipose tissue involvement may be an underrecognized feature of the disease. Herein, we report the case of a 16-year-old female carrying a previously described homozygous <i>TYMP</i> variant (c.1178_1201dup; p.Arg393_Val400dup), who presented during adolescence with generalized lipodystrophy, insulin resistance, hypertriglyceridemia, hepatic steatosis, and other metabolic complications. At diagnosis, she exhibited no overt neurological or gastrointestinal symptoms; however, electroneurography revealed subclinical peripheral neuropathy. This case broadens the phenotypic spectrum of TYMP-related disease by documenting a lipodystrophic and metabolic presentation associated with the p.Arg393_Val400dup variant. While <i>TYMP</i> mutations have been linked to lipodystrophy in rare cases, this specific variant had previously been reported only in the context of classical MNGIE, with no documented evidence of adipose tissue or metabolic derangement. Our findings highlight the importance of considering <i>TYMP</i> involvement in the differential diagnosis of atypical lipodystrophy syndromes, particularly when features suggest underlying mitochondrial dysfunction.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ezh2 Loss-of-Function Alters Zebrafish Cerebellum Development.","authors":"Mariette Hanot, Pamela Völkel, Xuefen Le Bourhis, Chann Lagadec, Pierre-Olivier Angrand","doi":"10.3390/ijms26199736","DOIUrl":"10.3390/ijms26199736","url":null,"abstract":"<p><p>EZH2, the catalytic subunit of polycomb repressive complex 2 (PRC2), plays a critical role in neural development by regulating gene expression through the trimethylation of lysine 27 on histone H3 (H3K27me3), which promotes chromatin remodeling and transcriptional repression. Although PRC2 is known to regulate cell fate specification and gliogenesis, its in vivo functions during vertebrate neurodevelopment, particularly at the level of neuronal subtype differentiation, remain incompletely understood. Here, we investigated the consequences of <i>ezh2</i> loss-of-function during zebrafish brain development, focusing on oligodendrocyte differentiation, cerebellar neurogenesis, and the formation of neurotransmitter-specific neuronal populations. Using whole-mount in situ hybridization, we found that <i>ezh2</i> inactivation does not alter the expression of oligodendrocyte lineage markers, indicating that early oligodendrocyte precursor cell specification and myelination are preserved. However, a significant reduction in cerebellar proliferation was observed in <i>ezh2</i>-deficient larvae, as evidenced by the downregulation of <i>pcna</i> and <i>cyclin A2</i>, while other brain regions remained unaffected. Notably, the expression of <i>atoh1c</i>, a key marker of glutamatergic cerebellar progenitors, was strongly reduced at 5 days post fertilization, suggesting a selective role for <i>ezh2</i> in maintaining cerebellar progenitor identity. This was associated with impaired differentiation of both glutamatergic granule cells and GABAergic Purkinje cells in specific cerebellar subregions. In contrast, the expression of markers for other major neurotransmitter systems remained unaffected, indicating a region-specific requirement for <i>ezh2</i> in neuronal development. Finally, behavioral analysis revealed a hyperlocomotor phenotype in <i>ezh2</i>^-/- larvae, consistent with cerebellar dysfunction. Together, these findings identify <i>ezh2</i> as a key regulator of progenitor maintenance and neuronal differentiation in the cerebellum, highlighting its crucial role in establishing functional cerebellar circuits.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein Corona as a Result of Interaction of Protein Molecules with Inorganic Nanoparticles.","authors":"Ruslan M Sarimov, Elena A Molkova, Alexander V Simakin, Alexey S Dorokhov, Sergey V Gudkov","doi":"10.3390/ijms26199771","DOIUrl":"10.3390/ijms26199771","url":null,"abstract":"<p><p>Currently, there is a growing interest in biomedical research in the use of inorganic nanoparticles for targeted drug delivery, as biosensors, and in theranostic applications. This review examines the interaction of inorganic nanoparticles with protein molecules depending on the chemical nature, size, and surface charge of the nanoparticles. The effect of protein and nanoparticle concentration, as well as their incubation time, is analyzed. The work focuses on the influence of parameters such as pH, ionic strength, and temperature on the interaction of nanoparticles with protein molecules. The following dependencies were studied in detail: the thickness of the protein corona as a function of nanoparticle size; the size of nanoparticles after interaction with protein as a function of protein and nanoparticle concentration; the distribution of zeta potentials in colloids of nanoparticles, proteins, and their mixtures. It has been shown that proteins and nanoparticles can influence each other's physicochemical properties. This can lead to the emergence of new biological properties in the system. Therefore, the adsorption of proteins onto nanoparticle surfaces can induce conformational changes. The probability of changing the protein structure increases when a covalent bond is formed between the nanoparticle and the protein molecule. Studies demonstrate that protein structure remains more stable with spherical nanoparticles than with rod-shaped or other high-curvature nanostructures. The results presented in the review demonstrate the possibility of adapting physiological responses to nanomaterials by changing the chemical composition of the surface of nanoparticles and their size and charge.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Custom Gene Panel Analysis Identifies Novel Polymorphisms Associated with Clopidogrel Response in Patients Undergoing Percutaneous Coronary Intervention with Stent.","authors":"Alba Antúnez-Rodríguez, Sonia García-Rodríguez, Ana Pozo-Agundo, Jesús Gabriel Sánchez-Ramos, Eduardo Moreno-Escobar, José Matías Triviño-Juárez, María Jesús Álvarez-Cubero, Luis Javier Martínez-González, Cristina Lucía Dávila-Fajardo","doi":"10.3390/ijms26199766","DOIUrl":"10.3390/ijms26199766","url":null,"abstract":"<p><p>Clopidogrel is widely used as an antiplatelet therapy for acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). Genetic factors influence variability in clopidogrel response, with non-functional <i>CYP2C19</i> alleles increasing the risk of major adverse cardiovascular events (MACEs). While <i>CYP2C19</i> genotype-guided therapy after PCI improves outcomes, MACEs persist at variable rates. Pharmacogenomics (PGx) has primarily focused on genes related to drug metabolism, but therapeutic failure may stem from individual disease predisposition. This study aims to identify novel genetic variants underlying adverse events after PCI despite PGx-guided therapy. A custom sequencing panel was analyzed in 244 ACS-PCI-stent patients and 99 controls without cardiovascular (CV) disease. Association analysis was performed independent of treatment and by prescribed treatment (clopidogrel or prasugrel), complemented by random forest models to predict risk during antiplatelet therapy. No polymorphism reached genomic significance, but in clopidogrel-treated patients, rs2472434 in <i>ABCA1</i>, related to altered lipid metabolism, was strongly associated with secondary CV events (<i>p</i> = 1.7 × 10^-3). Variants in the clopidogrel pathway, including <i>CYP2C19</i>, <i>ABCB1</i>, and <i>UGT2B7</i>, were also identified and may influence clopidogrel response. Predictive models incorporating these variants effectively discriminated patients with and without events (<i>p</i> = 0.02445). Our findings support combined genotyping of <i>CYP2C19</i> loss-of-function and <i>ABCB1 C3435T</i> variants to guide antiplatelet therapy and suggest additional targets, such as rs2472434 (<i>ABCA1</i>) and rs7439366 (<i>UGT2B7</i>), to improve risk prediction of adverse CV events. Therefore, the unexplained variability in clopidogrel response may be due to disease pathogenesis itself, highlighting the need for a paradigm shift in PGx studies.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of Galloyl-Flavonoid Conjugates as SARS-CoV-2 3CL^pro Inhibitors: Understanding Binding Interactions Through Computational Approaches.","authors":"Nopawit Khamto, Panida Boontawee, Vachira Choommongkol, Kritsada Pruksaphon, Suwicha Patnin, Nuttee Suree, Panchika Prangkio, Puttinan Meepowpan","doi":"10.3390/ijms26199742","DOIUrl":"10.3390/ijms26199742","url":null,"abstract":"<p><p>The emergence of SARS-CoV-2 in 2019 posed significant global public health challenges. One of the most promising targets for novel antiviral drug development is the SARS-CoV-2 main protease (3CL^pro). In this study, fragment molecular orbital (FMO) calculations were conducted to provide guidance for the structural modification of natural flavonoids, identifying the pyrogallol moiety as a key candidate. Natural flavonoids were chemically modified to generate 33 semi-synthetic derivatives through the introduction of various functional groups. Our findings revealed that the incorporation of a galloyl moiety significantly enhances anti-proteolytic activity against SARS-CoV-2 3CL^pro, achieving up to a 23-fold increase compared to the activity of the parent compounds. Notably, 7-<i>O</i>-galloyl-DMC (<b>40</b>) exhibited the highest anti-proteolytic activity in an enzymatic assay. Additionally, molecular dynamics simulations provided atomic-level insights into the interactions between the galloyl moiety and 3CL^pro. All galloylated flavonoid derivatives positioned their galloyl groups within the S1' sub-pocket, facilitating hydrogen bonding and π-interactions, particularly with Thr26 and Leu27. These findings underscore the potential of the galloyl moiety as a crucial structural element for enhancing the binding affinity of flavonoids with inhibitory activity against SARS-CoV-2 3CL^pro.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Role of Heat Shock Proteins in Neuroimmune Modulation in Rheumatoid Arthritis: Insights from a Rat Model.","authors":"Malak Fouani, Federica Scalia, Giuseppe Donato Mangano, Francesca Rappa, Wassim Abou-Kheir, Angelo Leone, Nada Lawand, Rosario Barone","doi":"10.3390/ijms26199743","DOIUrl":"10.3390/ijms26199743","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease affecting the joints, with neurogenic inflammation involving the nervous system being a hallmark of the condition. Treatments include medications such as disease-modifying antirheumatic drugs (DMARDs), corticosteroids, and biologics targeting inflammatory pathways. Yet, these treatments are not curative for RA. Heat Shock Proteins (HSPs) are molecular chaperones with immunoregulatory properties; however, their role is not yet fully understood, as these molecules may play a dual, pro- and anti-inflammatory role. In this study, we evaluated the protein expression levels of HSPs 27, 60, 70, and 90 in the synovial membrane and spinal cord of the RA rats' model to determine their roles during the disease course, both on the neurological and immunological levels. Furthermore, HSP levels have been evaluated in the spinal cord of control and RA rats' model after high and low doses of ketamine injection. Significant changes in Hsp60, 70, and 90 expression levels were observed only in the spinal cord of RA rats. We demonstrated that blocking N-methyl-D-aspartate receptors with ketamine can modulate spinal cord HSPs expression in RA rats and subsequently impact neurogenic inflammation and adult neurogenesis. This suggests that HSPs may be a promising target for RA treatment due to their complex immunomodulatory effects and potential interactions with the nervous system. Further research is needed to explore their therapeutic potential and develop effective interventions for RA.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating Reproducibility and Best Practices for Replicate Design in G-Quadruplex ChIP-Seq Studies.","authors":"Ke Xiao, Rongxin Zhang, Jing Tu","doi":"10.3390/ijms26199769","DOIUrl":"10.3390/ijms26199769","url":null,"abstract":"<p><p>G-quadruplex (G4) ChIP-Seq data are critical for studying the roles of G4 structures in various biological processes, yet their reproducibility remains systematically uncharacterized. In this study, we evaluated the consistency of in vivo G4 peaks across multiple replicates in three publicly available datasets. We observed considerable heterogeneity in peak calls, with only a minority of peaks shared across all replicates. To address this challenge, we compared three computational methods-IDR, MSPC, and ChIP-R-for assessing reproducibility and found that MSPC is the optimal solution in reconciling inconsistent signals in G4 ChIP-Seq data. We further demonstrated that employing at least three replicates significantly improved detection accuracy compared to conventional two-replicate designs, while four replicates proved sufficient to achieve reproducible outcomes, with diminishing returns beyond this number. Moreover, we showed that the reproducibility-aware analytical strategies can partially mitigate the adverse effects of low sequencing depth, though they do not fully substitute for high-quality data. Based on our findings, we recommend 10 million mapped reads as a minimum standard for G4 ChIP-Seq experiments, with 15 million or more reads being preferable for optimal results. Our study provides practical guidelines for experimental design and data analysis in G4 studies, emphasizing the importance of replication and robust bioinformatic strategies to enhance the reliability of genome-wide G4 mapping.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic Insights into Cytokinin-Regulated Leaf Senescence in Barley: Genotype-Specific Responses in Physiology and Protein Stability.","authors":"Ernest Skowron, Magdalena Trojak, Julia Szymkiewicz, Dominika Nawrot","doi":"10.3390/ijms26199749","DOIUrl":"10.3390/ijms26199749","url":null,"abstract":"<p><p>Cytokinins (CKs) are central regulators of leaf senescence, yet their cultivar-specific functions in cereals remain insufficiently understood. Here, we examined dark-induced senescence (DIS) in three barley (<i>Hordeum vulgare</i> L.) cultivars: Carina, Lomerit, and Bursztyn, focusing on responses to exogenous benzyladenine (BA) and inhibition of endogenous CK biosynthesis via the mevalonate (MVA) pathway using lovastatin (LOV). Bursztyn, a winter cultivar, displayed a previously uncharacterized stay-green phenotype, characterized by delayed chlorophyll and protein degradation and reduced sensitivity to BA with respect to chlorophyll retention. In contrast, Carina (spring) senesced rapidly but exhibited strong responsiveness to BA. Lomerit (winter) showed an intermediate phenotype, combining moderate natural resistance to senescence with clear responsiveness to BA. CK application suppressed SAG12 cysteine protease accumulation in all cultivars, serving as a marker of senescence and N remobilization, stabilized photosystem II efficiency, preserved photosynthetic proteins, and alleviated oxidative stress without promoting excessive energy dissipation. Although BA only partially mitigated the decline in net CO₂ assimilation, it sustained ribulose-1,5-bisphosphate regeneration, supported electron transport, and stabilized Rubisco and Rubisco activase. Moreover, LOV-based inhibition of the MVA pathway of CK biosynthesis revealed that endogenous CK contributions to senescence delay were most pronounced in Lomerit, moderate in Bursztyn, and negligible in Carina, indicating genotype-specific reliance on MVA-versus methylerythritol phosphate (MEP) pathway-derived CK pools. Collectively, these findings identify Bursztyn as a novel genetic resource for stay-green traits and demonstrate that BA delays DIS primarily by maintaining photosynthetic integrity and redox balance. The results highlight distinct regulatory networks shaping CK-mediated senescence responses in cereals, with implications for improving stress resilience and yield stability.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipid Peroxidation in Diabetic Kidney Disease: Mechanism and Natural Solution.","authors":"Yuxin Dong, Yanqing Tong","doi":"10.3390/ijms26199764","DOIUrl":"10.3390/ijms26199764","url":null,"abstract":"<p><p>Diabetic kidney disease (DKD), as one of the most serious microvascular complications of diabetes, is the main cause of end-stage renal disease in the world. Lipid peroxidation plays a crucial role in the development and progression of DKD. Under conditions of high glucose and insulin resistance, renal lipid metabolism disorders result in abnormal accumulation of polyunsaturated fatty acids (PUFAs), which undergo lipid peroxidation via free radical chain reactions to generate reactive aldehydes. These substances not only directly damage the cell structure but can also be used as signaling molecules that activate pathways related to inflammation, fibrosis, and ferroptosis, eventually leading to glomerular sclerosis and tubulointerstitial fibrosis. Natural products have shown considerable application prospects in the treatment of DKD due to their multi-functional properties, including anti-inflammatory, antioxidant, and lipid-metabolism-regulating effects. To elucidate this, we conducted a systematic review of the literature available in electronic databases (including PubMed, Web of Science, and Scopus, and Google Scholar) from January 2000 to May 2025. This study further discusses the therapeutic effect and mechanism of natural products targeting lipid peroxidation in DKD. The results indicate that natural products are promising anti-lipid peroxidation drugs. Further clinical trials will be necessary to verify the safety and effectiveness of these natural compounds in clinical applications, thereby laying the foundation for developing novel treatment strategies for DKD.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long Non-Coding RNA 1810026B05Rik Mediates Cerebral Ischemia/Reperfusion-Induced Neuronal Injury Through NF-κB Pathway Activation.","authors":"Hao Zhang, Meng Li, Jiayu Yao, Xuan Jiang, Junxiao Feng, Xingjuan Shi, Xiaoou Sun","doi":"10.3390/ijms26199756","DOIUrl":"10.3390/ijms26199756","url":null,"abstract":"<p><p>Cerebral ischemia/reperfusion (I/R) injury remains a significant contributor to adult neurological morbidity, primarily due to exacerbated neuroinflammation and cell apoptosis. These processes amplify brain damage through the release of various pro-inflammatory cytokines and pro-apoptotic mediators. Although long non-coding RNAs (lncRNAs) are increasingly recognized for their involvement in regulating diverse biological pathways, their precise role in cerebral I/R injury has not been fully elucidated. In the current study, transcriptomic profiling was conducted using a rat model of focal cerebral I/R, leading to the identification of lncRNA-1810026B05Rik-also referred to as CHASERR-as a novel lncRNA responsive to ischemic conditions. The elevated expression of this lncRNA was observed in mouse brain tissues subjected to middle cerebral artery occlusion followed by reperfusion (MCAO/R), as well as in primary cortical neurons derived from rats exposed to oxygen-glucose deprivation and subsequent reoxygenation (OGD/R). The results suggested that lncRNA-1810026B05RiK mediates the activation of the nuclear factor-kappaB (NF-κB) signaling pathway by physically binding to NF-kappa-B inhibitor alpha (IκBα) and promoting its phosphorylation, thus leading to neuroinflammation and neuronal apoptosis during cerebral ischemia/reperfusion. In addition, lncRNA-1810026B05Rik knockdown acts as an NF-κB inhibitor in the OGD/R and MCAO/R pathological processes, suggesting that lncRNA-1810026B05Rik downregulation exerts a protective effect on cerebral I/R injury. In summary, the lncRNA-1810026B05Rik has been identified as a critical regulator of neuronal apoptosis and inflammation through the activation of the NF-κB signaling cascade. This discovery uncovers a previously unrecognized role of 1810026B05Rik in the molecular mechanisms underlying ischemic stroke, offering valuable insights into disease pathology. Moreover, its involvement highlights its potential as a novel therapeutic target, paving the way for innovative treatment strategies for stroke patients.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}