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Association Between Scalp High-Frequency Oscillations and Burden of Amplitudes and Epileptiform Discharges (BASED) Scores in Infantile Epileptic Spasms Syndrome. 婴儿癫痫痉挛综合征中头皮高频振荡与振幅负担和癫痫样放电(BASED)评分之间的关系
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-05-10 DOI: 10.3390/biom15050697
Keisuke Maeda, Himari Tsuboi, Nami Hosoda, Junichi Fukumoto, Shiho Fujita, Shunta Yamaguchi, Naohiro Ichino, Keisuke Osakabe, Keiko Sugimoto, Gen Furukawa, Naoko Ishihara
{"title":"Association Between Scalp High-Frequency Oscillations and Burden of Amplitudes and Epileptiform Discharges (BASED) Scores in Infantile Epileptic Spasms Syndrome.","authors":"Keisuke Maeda, Himari Tsuboi, Nami Hosoda, Junichi Fukumoto, Shiho Fujita, Shunta Yamaguchi, Naohiro Ichino, Keisuke Osakabe, Keiko Sugimoto, Gen Furukawa, Naoko Ishihara","doi":"10.3390/biom15050697","DOIUrl":"10.3390/biom15050697","url":null,"abstract":"<p><p>Tools for measuring the likelihood of relapse in infantile epileptic spasms syndrome (IESS) treatment could aid clinicians in making critical management decisions. High-frequency oscillations (HFOs), transient bursts of electroencephalography (EEG) activity with frequencies beyond 80 Hz, are a new and promising noninvasive biomarker. The present study aimed to investigate the association between the Burden of Amplitudes and Epileptiform Discharges (BASED) scores, an interictal EEG grading scale for IESS, and scalp HFOs in patients with IESS. The study enrolled 50 patients, 25 with a clinical diagnosis of IESS and 25 without epilepsy. The percentage of patients with at least one scalp HFO detected, stratified by BASED scores, differed significantly: for BASED scores ≤ 2, 7.7%; for 3, 16.7%; for 4, 87.5%; and for 5, 100% (<i>p</i> < 0.001). Compared with BASED scores ≤ 2, the median scalp HFO detection rate was significantly highest for BASED scores of 5 (median [IQR]: 6.24 [2.25-8.32], <i>p</i> < 0.001), followed by BASED scores of 4. The scalp HFO detection rates showed a better performance in estimating patients with BASED scores of 4 and 5. It is hoped that scalp HFOs can be used as an objective indicator to validate the results of BASED scores.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156553","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}
引用次数: 0
LIFR-Mediated ERBB2 Signaling Is Essential for Successful Embryo Implantation in Mice. lifr介导的ERBB2信号是小鼠胚胎成功着床的必要条件。
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-05-10 DOI: 10.3390/biom15050698
Jumpei Terakawa, Sakura Nakamura, Mana Ohtomo, Saki Uehara, Yui Kawata, Shunsuke Takarabe, Hibiki Sugita, Takafumi Namiki, Atsuko Kageyama, Michiko Noguchi, Hironobu Murakami, Naomi Kashiwazaki, Junya Ito
{"title":"LIFR-Mediated ERBB2 Signaling Is Essential for Successful Embryo Implantation in Mice.","authors":"Jumpei Terakawa, Sakura Nakamura, Mana Ohtomo, Saki Uehara, Yui Kawata, Shunsuke Takarabe, Hibiki Sugita, Takafumi Namiki, Atsuko Kageyama, Michiko Noguchi, Hironobu Murakami, Naomi Kashiwazaki, Junya Ito","doi":"10.3390/biom15050698","DOIUrl":"10.3390/biom15050698","url":null,"abstract":"<p><p>In eutherian mammals, embryo implantation is a critical process for a successful pregnancy. In mice, the activation of the leukemia inhibitory factor (LIF) receptor-STAT3 signaling axis induces embryo adhesion and decidualization. The LIF receptor is believed to function as a heterodimer composed of LIFR (encoded by <i>Lifr</i>) and GP130 (encoded by <i>Il6st</i>); however, their distinct expression patterns in the uterine epithelium immediately prior to implantation suggest divergent functional roles. In this study, we generated uterine epithelium-specific <i>Lifr</i> knockout (<i>Lifr</i> eKO) mice and conducted a comprehensive gene expression analysis of the endometrium before implantation. We compared these results with those from uterine epithelium-specific <i>Gp130</i> knockout (<i>Gp130</i> eKO) mice. Similarly to <i>Gp130</i> eKO mice, <i>Lifr</i> eKO mice were completely infertile. We identified 299 genes with expression changes greater than twofold following gene deletion; among these, 31 genes were downregulated and 57 genes were upregulated in both eKO models. Many of the downregulated genes were previously implicated in uterine function. Hub gene analysis identified <i>Erbb2</i> and <i>c-Fos</i> as key regulators in both models. Further experiments using an ERBB2 inhibitor suggested that LIFR-ERBB2-mediated signaling plays a crucial role in embryo implantation.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156554","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}
引用次数: 0
Nav1.8 and Chronic Pain: From Laboratory Animals to Clinical Patients. Nav1.8与慢性疼痛:从实验动物到临床患者。
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-05-10 DOI: 10.3390/biom15050694
Yu-Feng Xie
{"title":"Nav1.8 and Chronic Pain: From Laboratory Animals to Clinical Patients.","authors":"Yu-Feng Xie","doi":"10.3390/biom15050694","DOIUrl":"10.3390/biom15050694","url":null,"abstract":"<p><p>As a subtype of voltage-gated sodium channel and predominantly expressed in the sensory neurons located in the dorsal root ganglion (DRG), the Nav1.8 channel encoded by the <i>SCN10A</i> gene is found to have different variants in patients suffering chronic pain or insensitivity to pain due to the gain-of-function or loss-of-function of Nav1.8 channels. In animal models of chronic pain, Nav1.8 is also verified to be involved, suggesting that Nav1.8 may be a potential target for treatment of chronic pain. Another voltage-gated sodium channel, Nav1.7, is also proposed to be a target for chronic pain, supported by clinical findings in patients and laboratory animal models; however, there is no Nav1.7-specific drug that has passed clinical trials, although they demonstrated satisfactory effects in laboratory animals. This discrepancy between clinical and preclinical studies may be related to the differences between humans and laboratory animals or due to the degeneracy in different sodium channels governing the DRG neuronal excitability, which is thought of as the underlying machinery of chronic pain and mostly studied. This review summarizes recent findings of Nav1.8 in chronic pain from clinics and laboratories and discusses the difference, which may be helpful for future investigation of Nav1.8 in chronic pain, considering the dilemma of the Nav1.7 channel in chronic pain.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156619","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}
引用次数: 0
The Insertion Domain of Mti2 Facilitates the Association of Mitochondrial Initiation Factors with Mitoribosomes in Schizosaccharomyces pombe. Mti2的插入结构域促进了裂糖酵母线粒体起始因子与线粒体糖体的关联。
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-05-10 DOI: 10.3390/biom15050695
Ying Luo, Jürg Bähler, Ying Huang
{"title":"The Insertion Domain of Mti2 Facilitates the Association of Mitochondrial Initiation Factors with Mitoribosomes in <i>Schizosaccharomyces pombe</i>.","authors":"Ying Luo, Jürg Bähler, Ying Huang","doi":"10.3390/biom15050695","DOIUrl":"10.3390/biom15050695","url":null,"abstract":"<p><p>Translation initiation in mitochondria involves unique mechanisms distinct from those in the cytosol or in bacteria. The <i>Schizosaccharomyces pombe</i> mitochondrial translation initiation factor 2 (Mti2) is the ortholog of human MTIF2, which plays a vital role in synthesizing proteins in mitochondria. Here, we investigate the insertion domain of Mti2, which stabilizes its interaction with the ribosome and is crucial for efficient translation initiation. Our results show that the insertion domain is critical for the proper folding and function of Mti2. The absence of the insertion domain disrupts cell growth and affects the expression of genes encoded by mitochondrial DNA. Additionally, we show that Mti2 physically interacts with the small subunits of mitoribosomes (mtSSU), and deletion of the insertion domain dissociates mitochondrial initiation factors from the mitoribosome, reducing the efficiency of mitochondrial translation. Altogether, these findings highlight the conserved role of the insertion domain in facilitating translation initiation in fission yeast and thus reveal shared principles of mitochondrial translation initiation in both fission yeast and humans.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156671","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}
引用次数: 0
Celebrating Ulrik Ringborg: Multi-Omics-Based Patient Stratification for Precision Cancer Treatment. 庆祝Ulrik Ringborg:基于多组学的精确癌症治疗患者分层。
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-05-10 DOI: 10.3390/biom15050693
Maria-Veronica Teleanu, Annika Schneider, Claudia R Ball, Mathias Felix Leber, Christoph Stange, Eva Krieghoff-Henning, Katja Beck, Christoph E Heilig, Simon Kreutzfeldt, Bernhard Kuster, Daniel B Lipka, Stefan Fröhling
{"title":"Celebrating Ulrik Ringborg: Multi-Omics-Based Patient Stratification for Precision Cancer Treatment.","authors":"Maria-Veronica Teleanu, Annika Schneider, Claudia R Ball, Mathias Felix Leber, Christoph Stange, Eva Krieghoff-Henning, Katja Beck, Christoph E Heilig, Simon Kreutzfeldt, Bernhard Kuster, Daniel B Lipka, Stefan Fröhling","doi":"10.3390/biom15050693","DOIUrl":"10.3390/biom15050693","url":null,"abstract":"<p><p>Precision oncology is becoming a mainstay in the standard of care for cancer patients. Recent technological advancements have significantly lowered the cost of various tumor profiling approaches, broadening the reach of molecular diagnostics and improving patient access to precision oncology. In parallel, drug development and discovery pipelines continue to evolve, driving targeted therapeutic options forward. Yet, not all patients harboring actionable molecular alterations respond to these interventions, and existing therapies do not cover the entire spectrum of potential molecular targets. In this review, we examine the current suite of omics technologies employed in clinical settings and underscore their roles in deepening our understanding of tumor biology and optimizing patient stratification for targeted treatments. We also highlight relevant precision oncology trials and share our own experiences using multi-omics data within a molecular tumor board framework. Finally, we discuss areas for future exploration aimed at propelling precision oncology to new heights.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156523","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}
引用次数: 0
Dynamics of Fatty Acid Composition in Lipids and Their Distinct Roles in Cardiometabolic Health. 脂质中脂肪酸组成的动态及其在心脏代谢健康中的独特作用。
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-05-10 DOI: 10.3390/biom15050696
Fiorenzo Toncan, Radha Raman Raj, Mi-Jeong Lee
{"title":"Dynamics of Fatty Acid Composition in Lipids and Their Distinct Roles in Cardiometabolic Health.","authors":"Fiorenzo Toncan, Radha Raman Raj, Mi-Jeong Lee","doi":"10.3390/biom15050696","DOIUrl":"10.3390/biom15050696","url":null,"abstract":"<p><p>Obesity and cardiometabolic diseases (CMDs) have reached epidemic levels. Dysregulation of lipid metabolism is a risk factor for obesity and CMDs. Lipids are energy substrates, essential components of cell membranes, and signaling molecules. Fatty acids (FAs) are the major components of lipids and are classified based on carbon chain length and number, position, and stereochemistry of double bonds. They exert differential impacts on CMDs, such that saturated fat increases risks while very-long-chain n-3 FAs provide benefits. The functionalities of FAs, modulating membrane properties, acting as ligands for receptors, and serving as precursors for lipid mediators, are vital for insulin signaling, lipid metabolism, oxidative stress, and inflammatory response, collectively contributing to cardiometabolic health. This review examines recent advances in the characteristics and functional properties of different FAs in lipid structures, signaling pathways, and cellular metabolism to better understand the differential roles of different types of FAs in obesity and cardiometabolic health.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12110056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156670","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}
引用次数: 0
Regulation of Protein Synthesis at the Translational Level: Novel Findings in Cardiovascular Biology. 蛋白合成在翻译水平的调控:心血管生物学的新发现。
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-05-09 DOI: 10.3390/biom15050692
Sergey Tsoy, Jiandong Liu
{"title":"Regulation of Protein Synthesis at the Translational Level: Novel Findings in Cardiovascular Biology.","authors":"Sergey Tsoy, Jiandong Liu","doi":"10.3390/biom15050692","DOIUrl":"10.3390/biom15050692","url":null,"abstract":"<p><p>Translational regulation plays a pivotal role in cardiac gene expression, influencing protein synthesis in response to physiological and pathological stimuli. Although transcription regulates gene expression, translation ultimately determines protein levels, making it a crucial research focus. In cardiomyocytes, disruptions in this process contribute to various cardiac diseases, including hypertrophy, fibrosis, dilated cardiomyopathy, ischemic heart disease, and diabetic cardiomyopathy. Emerging evidence highlights the significance of translational regulation across multiple cardiac cell types, such as cardiomyocytes and fibroblasts, and its role in disease progression. During cardiac remodeling, transcriptomic changes are often modest, suggesting that post-transcriptional mechanisms, particularly translation, play a dominant role in cellular adaptation. This review discusses key methodologies for studying translational regulation and novel mechanisms of translational regulation related to different cardiac pathologies and highlights relevant therapeutic avenues for targeting these pathways.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156460","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}
引用次数: 0
Modeling a Standard Loop-Mediated Isothermal Amplification Reaction and Its Modification Involving Additional Inner Primers. 一个标准环介导的等温扩增反应的模拟及其涉及额外内引物的修饰。
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-05-09 DOI: 10.3390/biom15050690
Liana U Akhmetzianova, Constantin I Mikhaylenko, Dmitry A Chemeris, Valery D Khairitdinov, Assol R Sakhabutdinova, Irek M Gubaydullin, Ravil R Garafutdinov, Alexey V Chemeris
{"title":"Modeling a Standard Loop-Mediated Isothermal Amplification Reaction and Its Modification Involving Additional Inner Primers.","authors":"Liana U Akhmetzianova, Constantin I Mikhaylenko, Dmitry A Chemeris, Valery D Khairitdinov, Assol R Sakhabutdinova, Irek M Gubaydullin, Ravil R Garafutdinov, Alexey V Chemeris","doi":"10.3390/biom15050690","DOIUrl":"10.3390/biom15050690","url":null,"abstract":"<p><p>Loop-mediated isothermal amplification (LAMP) was developed a quarter of a century ago, but it is still not exactly clear how this reaction proceeds. Only a few articles have focused on the kinetics of LAMP and the types of products formed. In this work, 10 types were identified and named. A basic dumbbell structure, Z6_dmb(1), consists of six zones and triggers the LAMP cycle. Due to self-priming, Z6_dmb(1) transforms into hairpin structure Z9_hp(1) and then into linearized strand Z9_li(1), carrying also strand Z6_dmb(2). Through similar transformations, it again generates strand Z6_dmb(1), completing the first LAMP cycle and starting a new one. The next stage of the exponential phase starts from two Z15_hp hairpin structures generated in the LAMP cycle, which next turn into Z15_li → Z27_hp → Z27_li → Z51_hp → and so forth. Modeling of a new type of the reaction, namely, pseudo-hemi-nested LAMP (phn-LAMP), was carried out. phn-LAMP involves three inner primers: two forward (FIP and extraFIP) and one backward inner primer, or vice versa. phn-LAMP has an advantage over LAMP involving loop or stem primers and over MIP-LAMP (multiple inner primers).</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12110036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156520","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}
引用次数: 0
Enhancing Ferroptosis in Lung Adenocarcinoma Cells via the Synergistic Action of Nonthermal Biocompatible Plasma and a Bioactive Phenolic Compound. 通过非热生物相容性等离子体和生物活性酚类化合物的协同作用增强肺腺癌细胞的铁凋亡。
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-05-09 DOI: 10.3390/biom15050691
Sabnaj Khanam, Young June Hong, Youngsun Kim, Eun Ha Choi, Ihn Han
{"title":"Enhancing Ferroptosis in Lung Adenocarcinoma Cells via the Synergistic Action of Nonthermal Biocompatible Plasma and a Bioactive Phenolic Compound.","authors":"Sabnaj Khanam, Young June Hong, Youngsun Kim, Eun Ha Choi, Ihn Han","doi":"10.3390/biom15050691","DOIUrl":"10.3390/biom15050691","url":null,"abstract":"<p><p>Para-coumaric acid (p-CA) is a phenolic compound that has antioxidant, anti-inflammatory, and anticancer properties which make it potential for cancer treatment. However, its effectiveness has been limited by poor solubility, rapid metabolism, and poor absorptivity. Nonthermal biocompatible pressure plasma (NBP) has gained attention as a cancer treatment due to its ability to generate reactive oxygen and nitrogen species (RONS), inducing oxidative stress that damages cancer cells. This study aimed to investigate the combined effect of NBP and p-CA on the induction of ferroptosis in lung adenocarcinoma via the GPX4, xCT, and NRF2 pathways. H460 and A549 lung adenocarcinoma cells as well as normal lung cells (MRC5) were treated with p-CA, NBP, and their combination. Cell movement, intracellular RONS levels, and lipid peroxidation, along with apoptosis and ferroptosis-related gene expression, were evaluated by co-treatment. Co-treatment also significantly elevated NO<sub>2</sub><sup>-</sup>, NO<sub>3</sub><sup>-</sup>, and H<sub>2</sub>O<sub>2</sub> levels and reduced cancer cell (H460, A549) viability (26, 31%) without affecting normal cells MRC5 (7%). Elevated MDA levels and changed expression of ferroptotic proteins indicated mitochondrial dysfunction, oxidative damage, lipid peroxidation, and DNA damage, which resulted in the induction of ferroptosis. These findings reveal a novel ferroptosis mechanism, emphasizing co-treatment for delivering bioavailable natural anticancer drugs.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156707","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}
引用次数: 0
MECP2 mRNA Profile in Brain Tissues from a Rett Syndrome Patient and Three Human Controls: Mutated Allele Preferential Transcription and In Situ RNA Mapping. Rett综合征患者和三个人类对照脑组织MECP2 mRNA谱:突变等位基因优先转录和原位RNA定位
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-05-08 DOI: 10.3390/biom15050687
Martina Mietto, Silvia Montanari, Maria Sofia Falzarano, Elisa Manzati, Paola Rimessi, Marina Fabris, Rita Selvatici, Francesca Gualandi, Marcella Neri, Fernanda Fortunato, Miryam Rosa Stella Foti, Stefania Bigoni, Marco Gessi, Marcella Vacca, Silvia Torelli, Joussef Hayek, Alessandra Ferlini
{"title":"<i>MECP2</i> mRNA Profile in Brain Tissues from a Rett Syndrome Patient and Three Human Controls: Mutated Allele Preferential Transcription and In Situ RNA Mapping.","authors":"Martina Mietto, Silvia Montanari, Maria Sofia Falzarano, Elisa Manzati, Paola Rimessi, Marina Fabris, Rita Selvatici, Francesca Gualandi, Marcella Neri, Fernanda Fortunato, Miryam Rosa Stella Foti, Stefania Bigoni, Marco Gessi, Marcella Vacca, Silvia Torelli, Joussef Hayek, Alessandra Ferlini","doi":"10.3390/biom15050687","DOIUrl":"10.3390/biom15050687","url":null,"abstract":"<p><p>Rett syndrome (RTT) is a rare X-linked dominant neurodevelopmental disorder caused by pathogenic variants in the methyl-CpG-binding protein 2 (<i>MECP2</i>) gene, which encodes a methyl-CpG-binding protein (MeCP2) that acts as a repressor of gene expression, crucial in neurons. Dysfunction of MeCP2 due to its pathogenic variants explains the clinical features of RTT. Here, we performed histological and RNA analyses on a post-mortem brain sample from an RTT patient carrying the p.Arg106Trp missense mutation. This patient is part of a cohort of 56 genetically and clinically characterized RTT patients, for whom we provide an overview of the mutation landscape. In the RTT brain specimen, RT-PCR analysis detected preferential transcription of the mutated mRNA. X-inactivation studies revealed a skewed X-chromosome inactivation ratio (95:5), supporting the transcriptional findings. We also mapped the <i>MECP2</i> transcript in control human brain regions (temporal cortex and cerebellum) using the RNAscope assay, confirming its high expression. This study reports the <i>MECP2</i> transcript representation in a post-mortem RTT brain and, for the first time, the in situ <i>MECP2</i> transcript localization in a human control brain, offering insights into how specific <i>MECP2</i> mutations may differentially impact neuronal functions. We suggest these findings are crucial for developing RNA-based therapies for Rett syndrome.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156477","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}
引用次数: 0
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