International Journal of Molecular Sciences最新文献_第6页

Genome-Wide Isoform Switching Reveals SR45-Mediated Splicing Control of Arabidopsis Leaf Senescence. 全基因组异构体开关揭示sr45介导的剪接控制拟南芥叶片衰老。

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-10-08 DOI: 10.3390/ijms26199784

Mohammed Albaqami, Ghaydaa Osamah Almaghrabi

{"title":"Genome-Wide Isoform Switching Reveals SR45-Mediated Splicing Control of Arabidopsis Leaf Senescence.","authors":"Mohammed Albaqami, Ghaydaa Osamah Almaghrabi","doi":"10.3390/ijms26199784","DOIUrl":"10.3390/ijms26199784","url":null,"abstract":"Leaf senescence is the final, programmed stage of leaf development, marked by nutrient remobilization and tightly regulated molecular events. Although alternative splicing has emerged as a major regulator of plant development, its role in isoform switching during leaf aging remains poorly understood. To address this, we conducted a genome-wide analysis of isoform switching in Arabidopsis, leveraging publicly available RNA-seq data from mature (16-day-old) and senescent (30-day-old) leaves, analyzed with the IsoformSwitchAnalyzeR package. Between these two developmental stages, we identified 269 genes exhibiting 377 significant isoform switches collectively predicted to alter protein localization, coding potential, and transcript stability. Experimental validation confirmed predicted switching at the PUS3 (Pseudouridine Synthase 3) locus, with sequence analysis revealing an age-dependent shift from mitochondrial-targeted to cytoplasmic isoforms. Gene Ontology enrichment analysis of switching genes revealed 82 significant terms, prominently associated with metabolism, gene expression, developmental regulation, and stress responses. Interestingly, we found nearly one-third of switching genes to overlap with known targets of the splicing factor SR45, with enrichment in pathways related to nucleotide and amino acid metabolism, energy production, and developmental processes. Correspondingly, dark-induced senescence assays revealed accelerated senescence in the sr45 mutant, confirming SR45's role in regulating leaf aging. Specific complementation of SR45's two isoforms revealed contrasting functions, with SR45.1 restoring normal senescence timing while SR45.2 failed to complement. Taken together, our findings demonstrate that differential isoform usage, orchestrated by specific splicing regulators, plays a critical role in leaf aging. This insight opens new avenues for manipulating senescence and engineering stay-green traits in crops.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145299805","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

Single-Nucleotide Polymorphisms, PITX2 and Abnormal Electrical Activity in Atrial Fibrillation. 房颤的单核苷酸多态性、PITX2与异常电活动。

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-10-08 DOI: 10.3390/ijms26199780

Verónica Jiménez-Sábado, Leif Hove-Madsen

{"title":"Single-Nucleotide Polymorphisms, PITX2 and Abnormal Electrical Activity in Atrial Fibrillation.","authors":"Verónica Jiménez-Sábado, Leif Hove-Madsen","doi":"10.3390/ijms26199780","DOIUrl":"10.3390/ijms26199780","url":null,"abstract":"Since single-nucleotide polymorphisms (SNPs) associated with increased risk of atrial fibrillation (AF) on chromosome 4q25 are located near the transcription factor PITX2, research has investigated relationships between SNPs, PITX2 activity and atrial function to improve risk stratification and identify new therapies. Although PITX2 levels are heterogeneous, most studies converge towards lower PITX2 levels in patients with AF, and a 4q25 SNP has been reported to reduce PITX2 expression. However, there are several SNPs at 4q25 that segregate independently, and patients carrying different SNPs respond differently to ablation therapy. On the other hand, atrial-specific deletion of Pitx2c mimics molecular and electrophysiological alterations observed in patients with AF. This includes microRNAs, signaling pathways, ion channels, calcium homeostasis, electrical remodeling, contraction and the response to pharmacological treatments. Moreover, mutations in the PITX2 homeodomain are associated with AF, PITX2 dysfunction or impaired calcium homeostasis. Interestingly, myocytes with the 4q25 risk allele rs13143308T display electrophysiological alterations similar to those reported in patients with AF or mice with heterozygous Pitx2c deletion. Moreover, carriers of rs13143308T respond poorly to ablation or antiarrhythmic drug therapy. Future research needs to establish how different 4q25 SNPs impact different PITX2 isoforms and the downstream regulation of atrial function.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300516","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

Zinc-Mediated Defenses Against Toxic Heavy Metals and Metalloids: Mechanisms, Immunomodulation, and Therapeutic Relevance. 锌介导的对有毒重金属和类金属的防御：机制、免疫调节和治疗相关性。

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-10-08 DOI: 10.3390/ijms26199797

Roopkumar Sangubotla, Shameer Syed, Anthati Mastan, Buddolla Anantha Lakshmi, Jongsung Kim

{"title":"Zinc-Mediated Defenses Against Toxic Heavy Metals and Metalloids: Mechanisms, Immunomodulation, and Therapeutic Relevance.","authors":"Roopkumar Sangubotla, Shameer Syed, Anthati Mastan, Buddolla Anantha Lakshmi, Jongsung Kim","doi":"10.3390/ijms26199797","DOIUrl":"10.3390/ijms26199797","url":null,"abstract":"Zinc (Zn), a naturally occurring trace element ubiquitous in the Earth's crust, soil, and water, is indispensable for human health due to its physiological and nutritive benefits. In this scenario, Zn is pivotal for maintaining homeostasis against toxic effects exerted by heavy metals (HMs) through bioaccumulation and metabolic interference. Zinc is an enticing cofactor for miscellaneous biochemical enzymes such as Zn metalloenzymes, which mediate crucial cellular processes, including cell proliferation, protein synthesis, immune modulation, epigenetic regulation, and nucleic acid synthesis. Recently, several research studies have focused on the thorough investigation of Zn supplementation in controlling HM toxicity by competing for binding sites and boosting protective mechanisms in humans. The current article discusses the upper limits for various toxic HMs in staple crop foods, as provided by globally recognized organizations. Clinical studies recommend a daily dose of 11 mg of Zn for healthy men and 8-12 mg for women in healthy and pregnancy conditions. However, during Zn deficiency, therapeutic supplementation is expected to be adjustable, and the dosage is increased from 15 to 30 mg daily. This review discusses the dysregulation of specific Zn importers and transporters (ZIPs/ZnTs) due to their clinical significance in immune system dysfunction as well as the progression of a myriad of cancers, including prostate, breast, and pancreas. Moreover, this review emphasizes indispensable in vitro and in vivo studies, as well as key molecular mechanisms related to Zn supplementation for treating toxicities exacerbated by HMs.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300617","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

Gepirone for Major Depressive Disorder: From Pharmacokinetics to Clinical Evidence: A Narrative Review. 孕酮治疗重度抑郁症：从药代动力学到临床证据：叙述性综述。

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-10-08 DOI: 10.3390/ijms26199805

Natalia Gałka, Emilia Tomaka, Julia Tomaszewska, Patrycja Pańczyszyn-Trzewik, Magdalena Sowa-Kućma

{"title":"Gepirone for Major Depressive Disorder: From Pharmacokinetics to Clinical Evidence: A Narrative Review.","authors":"Natalia Gałka, Emilia Tomaka, Julia Tomaszewska, Patrycja Pańczyszyn-Trzewik, Magdalena Sowa-Kućma","doi":"10.3390/ijms26199805","DOIUrl":"10.3390/ijms26199805","url":null,"abstract":"Gepirone, a selective 5-hydroxytryptamine (serotonin) 1A (5-HT1A) receptor agonist, offers a promising strategy for treating mood and anxiety disorders. The therapeutic importance of 5-HT1A modulation is well established, as these receptors regulate serotonergic neurotransmission both presynaptically, in the somatodendritic regions of raphe neurons, and postsynaptically, in structures including the hippocampus, neocortex, septum, amygdala, and hypothalamus. Gepirone exhibits a distinctive pharmacological profile, acting as a full agonist at presynaptic autoreceptors and a partial agonist at postsynaptic receptors, with high affinity for 5-HT1A and much lower affinity for 5-HT2A receptors. Its effects on serotonergic signaling are time-dependent. Acute administration suppresses serotonergic firing through autoreceptor activation, while chronic treatment induces autoreceptor desensitization, leading to enhanced 5-HT release in projection areas. This process is complemented by partial agonism at postsynaptic 5-HT1A receptors, which further supports long-term neuromodulation. This article provides an integrated overview of gepirone's mechanism of action, bridging receptor pharmacology, neurophysiological adaptations, and therapeutic implications. Particular emphasis is placed on the compound's unique dual role in regulating serotonergic tone over time, a feature that differentiates it from other 5-HT1A-targeting agents. By linking molecular mechanisms to clinical outcomes, we highlight gepirone's potential advantages in efficacy, safety, and tolerability compared with conventional antidepressants. This comprehensive perspective underscores gepirone as a paradigmatic example of selective 5-HT1A modulation and offers novel insights into the development of targeted treatments for depression and anxiety.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145299927","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

Hemoglobin-Based Oxygen Carriers: Selected Advances and Challenges in the Design of Safe Oxygen Therapeutics (A Focused Review). 基于血红蛋白的氧载体：安全氧疗法设计的选择进展和挑战（重点综述）。

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-10-08 DOI: 10.3390/ijms26199775

Waldemar Grzegorzewski, Anna Czerniecka-Kubicka, Katarzyna Gołda, Alicja Niedźwiedzka, Hanna Wollocko, Michał S Majewski, Joanna Wojtkiewicz

{"title":"Hemoglobin-Based Oxygen Carriers: Selected Advances and Challenges in the Design of Safe Oxygen Therapeutics (A Focused Review).","authors":"Waldemar Grzegorzewski, Anna Czerniecka-Kubicka, Katarzyna Gołda, Alicja Niedźwiedzka, Hanna Wollocko, Michał S Majewski, Joanna Wojtkiewicz","doi":"10.3390/ijms26199775","DOIUrl":"10.3390/ijms26199775","url":null,"abstract":"Blood transfusion is a routine yet resource-intensive medical procedure. Increasing global demand, limited donor availability, and logistical and ethical constraints have driven the search for adequate blood substitutes. Hemoglobin-based oxygen carriers (HBOCs) represent a promising class of therapeutics designed to mimic the oxygen transport function of red blood cells while overcoming the challenges of storage, compatibility, and infection risk. Despite decades of research, no HBOC has yet met all criteria for widespread clinical use. This review summarizes recent advances in the design and development of hemoglobin derivatives, with a focus on their biochemical properties, safety profiles, and oxygen delivery capabilities. We also discuss current limitations and translational barriers. The successful implementation of HBOCs could significantly improve transfusion strategies, especially in emergency medicine, military applications, and resource-limited settings. Continued innovation is essential to bring safe and effective oxygen therapeutics into routine clinical practice.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145299903","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

4-Phenylbutyric Acid Improves Gait Ability of UBAP1-Related Spastic Paraplegia Mouse Model: Therapeutic Potential for SPG80. 4-苯基丁酸改善ubap1相关痉挛性截瘫小鼠模型的步态能力：SPG80的治疗潜力

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-10-08 DOI: 10.3390/ijms26199779

Keisuke Shimozono, Yeon-Jeong Kim, Takanori Hata, Haitian Nan, Kozo Saito, Yasunori Mori, Yuji Ueno, Fujio Isono, Masaru Iwasaki, Schuichi Koizumi, Toshihisa Ohtsuka, Yoshihisa Takiyama

{"title":"4-Phenylbutyric Acid Improves Gait Ability of UBAP1-Related Spastic Paraplegia Mouse Model: Therapeutic Potential for SPG80.","authors":"Keisuke Shimozono, Yeon-Jeong Kim, Takanori Hata, Haitian Nan, Kozo Saito, Yasunori Mori, Yuji Ueno, Fujio Isono, Masaru Iwasaki, Schuichi Koizumi, Toshihisa Ohtsuka, Yoshihisa Takiyama","doi":"10.3390/ijms26199779","DOIUrl":"10.3390/ijms26199779","url":null,"abstract":"Spastic paraplegia 80 (SPG80), caused by mutations in ubiquitin-associated protein 1 (UBAP1), is a pure form of juvenile-onset hereditary spastic paraplegia (HSP) and leads to progressive motor dysfunction. Despite recent advances in the molecular analyses of HSP, disease-modifying therapy has not been established for HSP including SPG80. In the present study, we evaluated the therapeutic potential of 4-phenylbutyric acid (4-PBA), a chemical chaperone and histone deacetylase inhibitor, in Ubap1 knock-in (KI) mice expressing a disease-associated truncated UBAP1 variant. We found that 4-PBA administration significantly improved the motor performance of KI mice in the rotarod and beam walk tests, with maximal benefits achieved when given during pre- or early-symptomatic stages. Partial efficacy was also observed when treatment began after symptom onset in KI mice. Furthermore, 4-PBA attenuated spinal microglial activation and partially restored microglial morphology, although astrocytic reactivity remained unchanged. These findings support 4-PBA as a candidate therapeutic compound for SPG80 and highlight the potential of proteostasis-targeted interventions in HSPs.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145299958","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

Molecular Landscape of Prostate Cancer Across Age Groups: Impact on Prognosis and Treatment Outcomes. 跨年龄组前列腺癌的分子景观：对预后和治疗结果的影响。

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-10-08 DOI: 10.3390/ijms26199777

Magdalena Julita Orzechowska, Andrzej K Bednarek

{"title":"Molecular Landscape of Prostate Cancer Across Age Groups: Impact on Prognosis and Treatment Outcomes.","authors":"Magdalena Julita Orzechowska, Andrzej K Bednarek","doi":"10.3390/ijms26199777","DOIUrl":"10.3390/ijms26199777","url":null,"abstract":"Prostate cancer (PC) has long been considered a disease of older men. Still, a significant and concerning rise in diagnoses among younger men has revealed a biologically distinct and more aggressive clinical entity: early-onset prostate cancer (EO-PC). This comprehensive review synthesizes the molecular and clinical evidence to demonstrate that PC is not a single disease, but a collection of distinct entities delineated by patient age. EO-PC is characterized by a strong genetic component, unique fusion events like TMPRSS2-ERG, and a highly plastic phenotype driven by intense Notch signaling and a hybrid epithelial-to-mesenchymal transition. In stark contrast, late-onset prostate cancer (LO-PC) is defined by a higher mutational burden, an epigenetic \"field defect\" that accumulates with age, and a predominantly immunosuppressive tumor microenvironment. These profound biological differences have significant implications for diagnosis, prognosis, and therapeutic strategies. Traditional prognostic tools, such as the Gleason score, are often insufficient to capture the full spectrum of risk in younger men. The divergent molecular landscapes of EO-PC and LO-PC necessitate a fundamental shift from a standard approach to an age-aware precision medicine framework. This review highlights key therapeutic targets and underscores the critical need for a new paradigm in PC management to improve patient outcomes.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300269","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 Broad Clinical Spectrum of Metatropic Dysplasia: A Case Series and Literature Review. 变态发育不良的广泛临床谱：一个病例系列和文献回顾。

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-10-08 DOI: 10.3390/ijms26199783

Kiabeth Robles-Espinoza, Eduardo Esparza-García, Juan Ramón González García, María Teresa Magaña-Torres

{"title":"The Broad Clinical Spectrum of Metatropic Dysplasia: A Case Series and Literature Review.","authors":"Kiabeth Robles-Espinoza, Eduardo Esparza-García, Juan Ramón González García, María Teresa Magaña-Torres","doi":"10.3390/ijms26199783","DOIUrl":"10.3390/ijms26199783","url":null,"abstract":"Metatropic dysplasia is an autosomal dominant skeletal disorder characterized by progressive kyphoscoliosis, severe platyspondyly, pronounced metaphyseal enlargement, and shortening of the long bones. This condition is caused by pathogenic variants in the TRPV4 (Transient Receptor Potential Vanilloid 4) gene, which encodes a non-selective calcium channel involved in bone homeostasis. Variants in TRPV4 have been associated with two major disease groups: skeletal dysplasias and neuropathies, with recent findings indicating an overlap in their clinical features. We report three patients with metatropic dysplasia, each presenting a distinct severity profile. All exhibited a bell-shaped thorax, significant platyspondyly, and shortened long bones with broad metaphyses. Notably, patients 1 and 3 had more complex clinical courses, including seizures and global developmental delay. Genetic analysis revealed two different TRPV4 variants: p.Asn796del (patient 1) and p.Pro799Leu (patients 2 and 3). These cases illustrate variability in extra-skeletal manifestations, complications, and prognosis. In our patients with TRPV4-related disorders, the co-occurrence of neurological symptoms and skeletal abnormalities suggests a clinically heterogeneous spectrum consistent with a single disease rather than distinct entities. A comprehensive, multidisciplinary approach is essential to optimize management and improve the quality of life for patients.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300561","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

SPAchips: Microparticles Used for the Selective In Vitro Labelling of Microglia. SPAchips：用于小胶质细胞体外选择性标记的微粒。

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-10-08 DOI: 10.3390/ijms26199773

Justyna Gargas, Justyna Janowska, Beata Dabrowska-Bouta, Marta Sidoryk-Wegrzynowicz, Alberto M Hernández-Pinto, Rubén Miguez, Teresa Suárez, Lidia Struzynska, Joanna Sypecka

{"title":"SPAchips: Microparticles Used for the Selective In Vitro Labelling of Microglia.","authors":"Justyna Gargas, Justyna Janowska, Beata Dabrowska-Bouta, Marta Sidoryk-Wegrzynowicz, Alberto M Hernández-Pinto, Rubén Miguez, Teresa Suárez, Lidia Struzynska, Joanna Sypecka","doi":"10.3390/ijms26199773","DOIUrl":"10.3390/ijms26199773","url":null,"abstract":"Both basic and preclinical research, as well as the development of new therapies, require tools that allow for the selective labelling of specific cell types and the targeted delivery of drugs. The developed tools must then be validated in biological systems. In view of the lack of effective therapies for many neurodevelopmental disorders, including neonatal brain injuries, we decided to use the newly described, innovative SPAchips® (a4cell, Pozuelo de Alarcón, Spain) tool and test it in labelling neonatal rat neural cells. In our studies, rat primary cultures of neurons and glial cells (astrocytes, oligodendrocytes, and microglia) were incubated with different concentrations of SPAchips®. At selected time points, uptake of the tested microchips by particular cell types was assessed using lineage-specific antibodies and visualized using a confocal microscope. Additionally, the potential cytotoxicity of added microparticles was verified, as was the possibility of microglia activation. The study indicates that the tested microdevices selectively label neonatal rat microglia and can be a useful tool for visualizing this cell type, as well as a non-toxic tool for developing innovative strategies based on the functionalization of microparticles aimed at modulating neuroinflammatory processes.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145299898","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

Bladder Dysfunction in Sickle Cell Disease Is Associated with Inflammation and Oxidative Stress. 镰状细胞病患者膀胱功能障碍与炎症和氧化应激相关

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-10-08 DOI: 10.3390/ijms26199776

Dalila Andrade Pereira, Fabiano Beraldi Calmasini, Tammyris Helena Rebecchi Silveira, Danillo Andrade Pereira, Mariana G de Oliveira, Fernando Ferreira Costa, Fábio Henrique Silva

{"title":"Bladder Dysfunction in Sickle Cell Disease Is Associated with Inflammation and Oxidative Stress.","authors":"Dalila Andrade Pereira, Fabiano Beraldi Calmasini, Tammyris Helena Rebecchi Silveira, Danillo Andrade Pereira, Mariana G de Oliveira, Fernando Ferreira Costa, Fábio Henrique Silva","doi":"10.3390/ijms26199776","DOIUrl":"10.3390/ijms26199776","url":null,"abstract":"Bladder dysfunction, particularly overactive bladder (OAB), is increasingly recognized as a clinical concern in patients with sickle cell disease (SCD), yet its pathophysiological mechanisms remain poorly understood. This study investigated the relationship between oxidative stress, inflammation, and bladder dysfunction in the Townes transgenic SCD mouse model. Cystometric analysis revealed that SCD mice exhibit an OAB phenotype, characterized by increased frequencies of voiding and non-voiding contractions and reduced bladder compliance. In vitro functional assays demonstrated detrusor hypocontractility in SCD mice, associated with a significant reduction in carbachol- and EFS-induced contractions and downregulation of muscarinic M3 receptor expression. Purinergic signaling and calcium-dependent contractility remained preserved. Molecular analyses showed increased mRNA expression of NOX-2 and IL-1β, and elevated protein levels of 3-nitrotyrosine and myeloperoxidase (MPO) activity, indicating redox imbalance and chronic inflammation in bladder tissue. Together, these changes suggest that oxidative and nitrosative stress, combined with inflammation, contribute to bladder remodeling and dysfunction in SCD. This is the first study to characterize bladder alterations in Townes SCD mice, establishing this model as a valuable tool for investigating lower urinary tract complications in SCD. Our findings provide mechanistic insight into the genitourinary manifestations of SCD and identify redox and inflammatory pathways as potential therapeutic targets for bladder dysfunction in affected individuals.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145299981","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