International Journal of Molecular Sciences最新文献_第2页

A Multi-Modal Graph Neural Network Framework for Parkinson's Disease Therapeutic Discovery. 用于帕金森病治疗发现的多模态图神经网络框架。

IF 5.6 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-05-07 DOI: 10.3390/ijms26094453

Ömer Akgüller, Mehmet Ali Balcı, Gabriela Cioca

{"title":"A Multi-Modal Graph Neural Network Framework for Parkinson's Disease Therapeutic Discovery.","authors":"Ömer Akgüller, Mehmet Ali Balcı, Gabriela Cioca","doi":"10.3390/ijms26094453","DOIUrl":"10.3390/ijms26094453","url":null,"abstract":"Parkinson's disease (PD) is a complex neurodegenerative disorder lacking effective disease-modifying treatments. In this study, we integrated large-scale protein-protein interaction networks with a multi-modal graph neural network (GNN) to identify and prioritize multi-target drug repurposing candidates for PD. Network analysis and advanced clustering methods delineated functional modules, and a novel Functional Centrality Index was employed to pinpoint key nodes within the PD interactome. The GNN model, incorporating molecular descriptors, network topology, and uncertainty quantification, predicted candidate drugs that simultaneously target critical proteins implicated in lysosomal dysfunction, mitochondrial impairment, synaptic disruption, and neuroinflammation. Among the top hits were compounds such as dithiazanine, ceftolozane, DL-α-tocopherol, bromisoval, imidurea, medronic acid, and modufolin. These findings provide mechanistic insights into PD pathology and demonstrate that a polypharmacology approach can reveal repurposing opportunities for existing drugs. Our results highlight the potential of network-based deep learning frameworks to accelerate the discovery of multi-target therapies for PD and other multifactorial neurodegenerative diseases.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12072649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966219","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 Association of Resistin with Metabolic Health and Obesity in a Mexican-American Population. 抵抗素与墨西哥裔美国人代谢健康和肥胖的关系

IF 5.6 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-05-07 DOI: 10.3390/ijms26094443

Reem Al-Dallal, Keziah Thomas, MinJae Lee, Aysha Chaudhri, Eleanor Davis, Priyanka Vaidya, Miryoung Lee, Joseph B McCormick, Susan P Fisher-Hoch, Absalon D Gutierrez

{"title":"The Association of Resistin with Metabolic Health and Obesity in a Mexican-American Population.","authors":"Reem Al-Dallal, Keziah Thomas, MinJae Lee, Aysha Chaudhri, Eleanor Davis, Priyanka Vaidya, Miryoung Lee, Joseph B McCormick, Susan P Fisher-Hoch, Absalon D Gutierrez","doi":"10.3390/ijms26094443","DOIUrl":"10.3390/ijms26094443","url":null,"abstract":"Research on the relationship between resistin levels, metabolic health, and obesity has produced inconsistent findings across different ethnic groups, making it unclear whether lower resistin levels are associated with these conditions in Mexican-Americans. This cross-sectional study investigated the relationship between resistin, metabolic health, and obesity in an adult Mexican-American cohort (n = 1511) using multivariable linear regression analysis. Related adipokines (leptin and adiponectin) were measured simultaneously. Participants were categorized into four groups by metabolic health (healthy/unhealthy) and obesity (obese/non-obese) status. \"Metabolically unhealthy\" was defined as ≥2 cardiometabolic abnormalities. Obesity was defined as a BMI ≥ 30 kg/m2. We also investigated the associations of related proinflammatory cytokines, demographic/anthropometric variables, and medications with each outcome variable of interest. The results showed no statistically significant differences in resistin levels between the groups. Leptin was higher and adiponectin was lower in groups with obesity and/or metabolically unhealthy status. The resistin findings contrast studies in other populations, while other leptin and adiponectin findings confirm those seen in many ethnic groups. Thiazolidinedione use was associated with lower resistin, confirming earlier research. These findings suggest that resistin's role in metabolic health may be different in Mexican-Americans compared to other populations.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12072545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000391","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

Mitochondrial Dysfunction in Genetic and Non-Genetic Parkinson's Disease. 遗传性和非遗传性帕金森病的线粒体功能障碍。

IF 5.6 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-05-07 DOI: 10.3390/ijms26094451

Martina Lucchesi, Letizia Biso, Marco Bonaso, Biancamaria Longoni, Bianca Buchignani, Roberta Battini, Filippo Maria Santorelli, Stefano Doccini, Marco Scarselli

{"title":"Mitochondrial Dysfunction in Genetic and Non-Genetic Parkinson's Disease.","authors":"Martina Lucchesi, Letizia Biso, Marco Bonaso, Biancamaria Longoni, Bianca Buchignani, Roberta Battini, Filippo Maria Santorelli, Stefano Doccini, Marco Scarselli","doi":"10.3390/ijms26094451","DOIUrl":"10.3390/ijms26094451","url":null,"abstract":"Mitochondrial dysfunction is a hallmark of Parkinson's disease (PD) pathogenesis, contributing to increased oxidative stress and impaired endo-lysosomal-proteasome system efficiency underlying neuronal injury. Genetic studies have identified 19 monogenic mutations-accounting for ~10% of PD cases-that affect mitochondrial function and are associated with early- or late-onset PD. Early-onset forms typically involve genes encoding proteins essential for mitochondrial quality control, including mitophagy and structural maintenance, while late-onset mutations impair mitochondrial dynamics, bioenergetics, and trafficking. Atypical juvenile genetic syndromes also exhibit mitochondrial abnormalities. In idiopathic PD, environmental neurotoxins such as pesticides and MPTP act as mitochondrial inhibitors, disrupting complex I activity and increasing reactive oxygen species. These converging pathways underscore mitochondria as a central node in PD pathology. This review explores the overlapping and distinct mitochondrial mechanisms in genetic and non-genetic PD, emphasizing their role in neuronal vulnerability. Targeting mitochondrial dysfunction finally offers a promising therapeutic avenue to slow or modify disease progression by intervening at a key point of neurodegenerative convergence.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12072996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014952","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

High Concentrations of Circulating 2PY and 4PY-Potential Risk Factor of Cardiovascular Disease in Patients with Chronic Kidney Disease. 血液中高浓度2PY和4py -慢性肾病患者心血管疾病的潜在危险因素

IF 5.6 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-05-07 DOI: 10.3390/ijms26094463

Agnieszka Dettlaff-Pokora, Julian Swierczynski

{"title":"High Concentrations of Circulating 2PY and 4PY-Potential Risk Factor of Cardiovascular Disease in Patients with Chronic Kidney Disease.","authors":"Agnieszka Dettlaff-Pokora, Julian Swierczynski","doi":"10.3390/ijms26094463","DOIUrl":"10.3390/ijms26094463","url":null,"abstract":"Recently published data indicate that elevated circulating concentrations of N1-methyl-2-pyridone-5-carboxamide (2PY, also described as Met2PY) and N1-methyl-4-pyridone-5-carboxamide (4PY, also described as Met4PY), terminal catabolites of nicotinamide adenine dinucleotide (NAD+), are associated with cardiovascular disease (CVD) risk in humans. Previously, we and the others have shown that patients with advanced stages of chronic kidney disease (CKD) exhibit several-fold higher circulating 2PY and 4PY concentrations compared to healthy subjects or patients in the early stages of the disease. It is also well documented that patients with advanced CKD stages exhibit markedly elevated CVD risk, which is the main cause of premature death (in these patients). Therefore, we hypothesize that high concentrations of circulating 2PY and 4PY are important factors that may contribute to cardiovascular events and, ultimately, premature death in CKD patients. However, further, accurately controlled clinical research is needed to provide definitive answers concerning the role of 2PY and 4PY in CVD risk in CKD patients. Moreover, we are dealing with some issues related to the use of NAD+ precursors (NAD+ boosters) as drugs (also in CKD patients) and/or supplements. Due to the increase in circulating 2PY and 4PY levels during treatment with NAD+ boosters, these precursors should be used with caution, especially in patients with increased CVD risk.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12072460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144016584","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

Electrochemical Boron Detection with Ferrocene and Catechol-Functionalized Cyclodextrin Inclusion Complex. 二茂铁和儿茶酚功能化环糊精包合物电化学检测硼。

IF 5.6 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-05-07 DOI: 10.3390/ijms26094432

Kai Sato, Hiroshi Kimoto, Takeshi Hashimoto

{"title":"Electrochemical Boron Detection with Ferrocene and Catechol-Functionalized Cyclodextrin Inclusion Complex.","authors":"Kai Sato, Hiroshi Kimoto, Takeshi Hashimoto","doi":"10.3390/ijms26094432","DOIUrl":"10.3390/ijms26094432","url":null,"abstract":"We demonstrate a rapid and sensitive boron detection method through current amplification mediated by supramolecular interaction. Oxidation peak currents obtained by cyclic voltammetry (CV) measurements of a ferrocene/catechol-functionalized β-cyclodextrin inclusion complex were amplified through an EC' reaction (where EC' denotes an electrochemical step followed by a catalytic chemical step). However, the amplified current was decreased by boric acid (the primary form of boron in water) addition at pH 8.6 owing to interactions of boron with the cis-diol structure of dihydroxybenzoic acid-β-cyclodextrin and ferrocene for ester formation. We determined the optimum CyD functionalization sites and measurement conditions and obtained a limit of detection of 0.16 mg B L-1 for ferrocene/3,4-dihydroxybenzoic acid-β-cyclodextrin (Fc/3,4-DHBA-β-CyD). The binding constant (assuming a 1:1 binding model) for the interaction between Fc/3,4-DHBA-β-CyD and boric acid was estimated to be approximately 1500 M-1. Boron concentrations in spiked real samples showed good recoveries and linear calibration curves. The electrochemical response of this system was not significantly affected by the presence of other anions or cations. We also found that an aqueous solution of 3,4-DHBA-β-CyD remained stable for at least 112 days.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12072688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001585","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 Role of Salicylic Acid in Activating Plant Stress Responses-Results of the Past Decade and Future Perspectives. 水杨酸在激活植物胁迫反应中的作用——近十年的研究结果及展望

IF 5.6 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-05-07 DOI: 10.3390/ijms26094447

Kincső Decsi, Mostafa Ahmed, Donia Abdul-Hamid, Zoltán Tóth

引用次数: 0

Interaction Between Neutrophils and Elements of the Blood-Brain Barrier in the Context of Multiple Sclerosis and Ischemic Stroke. 中性粒细胞与血脑屏障元素在多发性硬化症和缺血性中风中的相互作用。

IF 5.6 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-05-07 DOI: 10.3390/ijms26094437

Anna Nowaczewska-Kuchta, Dominika Ksiazek-Winiarek, Andrzej Glabinski

{"title":"Interaction Between Neutrophils and Elements of the Blood-Brain Barrier in the Context of Multiple Sclerosis and Ischemic Stroke.","authors":"Anna Nowaczewska-Kuchta, Dominika Ksiazek-Winiarek, Andrzej Glabinski","doi":"10.3390/ijms26094437","DOIUrl":"10.3390/ijms26094437","url":null,"abstract":"The blood-brain barrier (BBB) is a semi-permeable membrane in physiological conditions, but in pathologies like multiple sclerosis (MS) and ischemic stroke (IS), its permeability increases. In this review, we focus on neutrophils and their interaction with cellular components of the BBB: endothelial cells (EC), pericytes (PC), and astrocytes (AC). Nowadays, neutrophils receive more attention, mostly due to advanced research techniques that show the complexity of their population. Additionally, neutrophils have the ability to secrete extracellular vesicles (EVs), reactive oxygen species (ROS) and cytokines, which both destroy and restore the BBB. Astrocytes, PCs, and ECs also have dual roles in the pathogenesis of MS and IS. The interaction between neutrophils and cellular components of the BBB provides us with a wider insight into the pathogenesis of common diseases in the central nervous system. Further, we comprehensively review knowledge about the influence of neutrophils on the BBB in the context of MS and IS. Moreover, we describe new therapeutic strategies for patients with MS and IS like cell-based therapies and therapies that use the neutrophil function.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12072651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969029","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

Impact of Vehicle Composition on Solubility, Autoclave Sterilization Stability, and Antibacterial Activity of Ciprofloxacin Hydrochloride Ear Drops. 载体组成对盐酸环丙沙星滴耳液溶解度、灭菌稳定性及抗菌活性的影响。

IF 5.6 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-05-07 DOI: 10.3390/ijms26094458

Weerasak Samee, Sarin Tadtong, Wanna Eiamart, Pattaraporn Singwiset, Sirivimon Yingyomsarn, Patcharawee Nunthanavanit

{"title":"Impact of Vehicle Composition on Solubility, Autoclave Sterilization Stability, and Antibacterial Activity of Ciprofloxacin Hydrochloride Ear Drops.","authors":"Weerasak Samee, Sarin Tadtong, Wanna Eiamart, Pattaraporn Singwiset, Sirivimon Yingyomsarn, Patcharawee Nunthanavanit","doi":"10.3390/ijms26094458","DOIUrl":"10.3390/ijms26094458","url":null,"abstract":"This research focused on the formulation of ciprofloxacin hydrochloride ear drops for the treatment of acute otitis externa, caused by pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa. The study aimed to enhance the solubility of ciprofloxacin at physiological pH and improve its stability during autoclave sterilization by employing polyalcohol vehicle systems composed of deionized water, glycerin, and propylene glycol. Formulations containing 0.33% w/v ciprofloxacin HCl were evaluated for solubility within a pH range of 4.0 to 7.0 and underwent autoclave sterilization to assess their chemical stability and antibacterial efficacy. Following sterilization, the formulations were stored at 25 °C in amber containers for a duration of 180 days. High-performance liquid chromatography (HPLC) was utilized to evaluate chemical stability, while antibacterial activity was determined using the disk diffusion method. The results demonstrated that glycerin and propylene glycol effectively inhibited ciprofloxacin precipitation at physiological pH. The ciprofloxacin content decreased by less than 3.58% while preserving antimicrobial efficacy against S. aureus and P. aeruginosa. Both formulations retained over 90% of their labeled drug content, indicating a minimum shelf life of 180 days under the specified storage conditions.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12072675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005869","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 Feud over Lactate and Its Role in Brain Energy Metabolism: An Unnecessary Burden on Research and the Scientists Who Practice It. 关于乳酸及其在大脑能量代谢中的作用的争论：对研究和实践它的科学家来说是不必要的负担。

IF 5.6 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-05-07 DOI: 10.3390/ijms26094429

Avital Schurr

引用次数: 0

Hsa-miR-21-5p and Hsa-miR-145-5p Expression: From Normal Tissue to Malignant Changes-Context-Dependent Correlation with Estrogen- and Hypoxia-Vascularization-Related Pathways Genes: A Pilot Study. Hsa-miR-21-5p和Hsa-miR-145-5p表达：从正常组织到恶性变化-与雌激素和缺氧血管化相关通路基因的背景依赖性相关性：一项初步研究

IF 5.6 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-05-07 DOI: 10.3390/ijms26094461

Mateusz Górecki, Aleksandra Żbikowska, Małgorzata Tokłowicz, Stefan Sajdak, Monika Englert-Golon, Mirosław Andrusiewicz

{"title":"Hsa-miR-21-5p and Hsa-miR-145-5p Expression: From Normal Tissue to Malignant Changes-Context-Dependent Correlation with Estrogen- and Hypoxia-Vascularization-Related Pathways Genes: A Pilot Study.","authors":"Mateusz Górecki, Aleksandra Żbikowska, Małgorzata Tokłowicz, Stefan Sajdak, Monika Englert-Golon, Mirosław Andrusiewicz","doi":"10.3390/ijms26094461","DOIUrl":"10.3390/ijms26094461","url":null,"abstract":"Ovarian cancer (OC) is a severe gynecological malignancy with a high mortality rate among women worldwide. It is often diagnosed at advanced stages due to the lack of effective screening methods. This study investigated the expression patterns of microRNAs (miRNAs) hsa-miR-21-5p and hsa-miR-145-5p as potential OC prognostic and diagnostic biomarkers and their correlation with estrogen-dependent (ESR1 & 2, PELP1 and c-SRC) and hypoxia-neovascularization-induced (HIF1A, EPAS1, and VEGFA) pathway genes. Tissue samples obtained from twenty patients with confirmed ovarian cancer and twenty controls were analyzed using quantitative polymerase chain reaction (qPCR) to examine miRNA and mRNA levels. The qPCR analysis revealed significantly higher hsa-miR-21-5p and lower hsa-miR-145-5p expression in OC tissues than controls. Moreover, a significant trend was observed in hsa-miR-21-5p and hsa-miR-145-5p expression levels across normal, non-cancerous changes and malignant ovarian tissues. The hsa-miR-21-5p showed better diagnostic potential than hsa-miR-145-5p. We also observed inconsistent correlations in hsa-miR-21-5p and hsa-mir-145-5p and estrogen-related and hypoxia-neovascularization-dependent genes in ovarian cancer across all groups. This suggests that the relationship between these miRNAs and the selected genes is context-specific. Our findings suggest that hsa-miR-21-5p and hsa-miR-145-5p expression levels may be prognostic or diagnostic markers for ovarian cancer patients.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12072406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001636","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