International Journal of Molecular Sciences最新文献

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SMURF1-Induced Ubiquitination of FTH1 Disrupts Iron Homeostasis and Suppresses Myogenesis.
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2025-02-06 DOI: 10.3390/ijms26031390
Xia Xiong, Wen Li, Chunlin Yu, Mohan Qiu, Zengrong Zhang, Chenming Hu, Shiliang Zhu, Li Yang, Han Pen, Xiaoyan Song, Jialei Chen, Bo Xia, Shunshun Han, Chaowu Yang
{"title":"SMURF1-Induced Ubiquitination of FTH1 Disrupts Iron Homeostasis and Suppresses Myogenesis.","authors":"Xia Xiong, Wen Li, Chunlin Yu, Mohan Qiu, Zengrong Zhang, Chenming Hu, Shiliang Zhu, Li Yang, Han Pen, Xiaoyan Song, Jialei Chen, Bo Xia, Shunshun Han, Chaowu Yang","doi":"10.3390/ijms26031390","DOIUrl":"10.3390/ijms26031390","url":null,"abstract":"<p><p>Ferritin heavy chain 1 (FTH1) is pivotal in the storage, release, and utilization of iron, plays a crucial role in the ferroptosis pathway, and exerts significant impacts on various diseases. Iron influences skeletal muscle development and health by promoting cell growth, ensuring energy metabolism and ATP synthesis, maintaining oxygen supply, and facilitating protein synthesis. However, the precise molecular mechanisms underlying iron's regulation of skeletal muscle growth and development remain elusive. In this study, we demonstrated that the conditional knockout (cKO) of FTH1 in skeletal muscle results in muscle atrophy and impaired exercise endurance. In vitro studies using FTH1 cKO myoblasts revealed notable decreases in GSH concentrations, elevated levels of lipid peroxidation, and the substantial accumulation of Fe<sup>2+</sup>, collectively implying the induction of ferroptosis. Mechanistically, E3 ubiquitin-protein ligase SMURF1 (SMURF1) acts as an E3 ubiquitin ligase for FTH1, thereby facilitating the ubiquitination and subsequent degradation of FTH1. Consequently, this activation of the ferroptosis pathway by SMURF1 impedes myoblast differentiation into myotubes. This study identifies FTH1 as a novel regulator of muscle cell differentiation and skeletal muscle development, implicating its potential significance in maintaining skeletal muscle health through the regulation of iron homeostasis.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11818545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407842","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
CITE-Seq Analysis Reveals a Differential Natural Killer Cell SPON2 Expression in Cardiovascular Disease Patients Impacted by Human-Cytomegalovirus Serostatus and Diabetes.
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2025-02-06 DOI: 10.3390/ijms26031369
Sujit Silas Armstrong, Daniel G Chen, Sunil Kumar, James R Heath, Matthew J Feinstein, John R Greenland, Daniel R Calabrese, Lewis L Lanier, Klaus Ley, Avishai Shemesh
{"title":"CITE-Seq Analysis Reveals a Differential Natural Killer Cell <i>SPON2</i> Expression in Cardiovascular Disease Patients Impacted by Human-Cytomegalovirus Serostatus and Diabetes.","authors":"Sujit Silas Armstrong, Daniel G Chen, Sunil Kumar, James R Heath, Matthew J Feinstein, John R Greenland, Daniel R Calabrese, Lewis L Lanier, Klaus Ley, Avishai Shemesh","doi":"10.3390/ijms26031369","DOIUrl":"10.3390/ijms26031369","url":null,"abstract":"<p><p>Coronary artery disease (CAD) is linked to atherosclerosis plaque formation. In pro-inflammatory conditions, human Natural Killer (NK) cell frequencies in blood or plaque decrease; however, NK cells are underexplored in CAD pathogenesis, inflammatory mechanisms, and CAD comorbidities, such as human cytomegalovirus (HCMV) infection and diabetes. Analysis of PBMC CITE-seq data from sixty-one CAD patients revealed higher blood NK cell <i>SPON2</i> expression in CAD patients with higher stenosis severity. Conversely, NK cell <i>SPON2</i> expression was lower in pro-inflammatory atherosclerosis plaque tissue with an enriched adaptive NK cell gene signature. In CAD patients with higher stenosis severity, peripheral blood NK cell <i>SPON2</i> expression was lower in patients with high HCMV-induced adaptive NK cell frequencies and corresponded to lower PBMC <i>TGFβ</i> transcript expression with dependency on diabetes status. These results suggest that high NK cell <i>SPON2</i> expression is linked to atherosclerosis pro-homeostatic status and may have diagnostic and prognostic implications in cardiovascular disease.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11818894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407521","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 Gut Microbiota-Derived Trimethylamine N-Oxide in the Pathogenesis and Treatment of Mild Cognitive Impairment.
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2025-02-06 DOI: 10.3390/ijms26031373
Haihua Xie, Jia Jiang, Sihui Cao, Xuan Xu, Jingyin Zhou, Ruhan Zhang, Bo Huang, Penghui Lu, Liang Peng, Mi Liu
{"title":"The Role of Gut Microbiota-Derived Trimethylamine N-Oxide in the Pathogenesis and Treatment of Mild Cognitive Impairment.","authors":"Haihua Xie, Jia Jiang, Sihui Cao, Xuan Xu, Jingyin Zhou, Ruhan Zhang, Bo Huang, Penghui Lu, Liang Peng, Mi Liu","doi":"10.3390/ijms26031373","DOIUrl":"10.3390/ijms26031373","url":null,"abstract":"<p><p>Mild cognitive impairment (MCI) represents a transitional stage between normal aging and dementia, often considered critical for dementia prevention. Despite its significance, no effective clinical treatment for MCI has yet been established. Emerging evidence has demonstrated a strong association between trimethylamine-N-oxide (TMAO), a prominent metabolite derived from the gut microbiota, and MCI, highlighting its potential as a biomarker and therapeutic target. TMAO has been implicated in increasing MCI risk through its influence on factors such as hypertension, cardiovascular disease, depression, diabetes, and stroke. Moreover, it contributes to MCI by promoting oxidative stress, disrupting the blood-brain barrier, impairing synaptic plasticity, inducing inflammation, causing mitochondrial metabolic disturbances, and facilitating abnormal protein aggregation. This review further explores therapeutic strategies targeting TMAO to mitigate MCI progression.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11818489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407916","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
Atherosclerosis: A Comprehensive Review of Molecular Factors and Mechanisms.
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2025-02-06 DOI: 10.3390/ijms26031364
Vasiliki Tasouli-Drakou, Ian Ogurek, Taha Shaikh, Marc Ringor, Michael V DiCaro, KaChon Lei
{"title":"Atherosclerosis: A Comprehensive Review of Molecular Factors and Mechanisms.","authors":"Vasiliki Tasouli-Drakou, Ian Ogurek, Taha Shaikh, Marc Ringor, Michael V DiCaro, KaChon Lei","doi":"10.3390/ijms26031364","DOIUrl":"10.3390/ijms26031364","url":null,"abstract":"<p><p>Atherosclerosis, a condition characterized by the accumulation of lipids and a culprit behind cardiovascular events, has long been studied. However, in recent years, there has been an increase in interest in its initiation, with researchers shifting focus from traditional pathways involving the vascular infiltration of oxidized lipids and towards the novel presence of chronic inflammatory pathways. The accumulation of pro-inflammatory cytokines, in combination with the activation of transcription factors, creates a positive feedback loop that drives the creation and progression of atherosclerosis. From the upregulation of the nod-like receptor protein 3 (NLRP3) inflammasome and the Notch and Wnt pathways to the increased expression of VEGF-A and the downregulation of connexins Cx32, Cx37, and Cx40, these processes contribute further to endothelial dysfunction and plaque formation. Herein, we aim to provide insight into the molecular pathways and mechanisms implicated in the initiation and progression of atherosclerotic plaques, and to review the risk factors associated with their development.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11818631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407189","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
Differential Regulation of miRNA and Protein Profiles in Human Plasma-Derived Extracellular Vesicles via Continuous Aerobic and High-Intensity Interval Training.
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2025-02-06 DOI: 10.3390/ijms26031383
Zhenghao Wang, Yiran Ou, Xinyue Zhu, Ye Zhou, Xiaowei Zheng, Meixia Zhang, Sheyu Li, Shao-Nian Yang, Lisa Juntti-Berggren, Per-Olof Berggren, Xiaofeng Zheng
{"title":"Differential Regulation of miRNA and Protein Profiles in Human Plasma-Derived Extracellular Vesicles via Continuous Aerobic and High-Intensity Interval Training.","authors":"Zhenghao Wang, Yiran Ou, Xinyue Zhu, Ye Zhou, Xiaowei Zheng, Meixia Zhang, Sheyu Li, Shao-Nian Yang, Lisa Juntti-Berggren, Per-Olof Berggren, Xiaofeng Zheng","doi":"10.3390/ijms26031383","DOIUrl":"10.3390/ijms26031383","url":null,"abstract":"<p><p>Both continuous aerobic training (CAT) and high-intensity interval training (HIIT) are recommended to promote health and prevent diseases. Exercise-induced circulating extracellular vesicles (EX-EVs) have been suggested to play essential roles in mediating organ crosstalk, but corresponding molecular mechanisms remain unclear. To assess and compare the systemic effects of CAT and HIIT, five healthy male volunteers were assigned to HIIT and CAT, with a 7-day interval between sessions. Plasma EVs were collected at rest or immediately after each training section, prior to proteomics and miRNA profile analysis. We found that the differentially expressed (DE) miRNAs in EX-EVs were largely involved in the regulation of transcriptional factors, while most of the DE proteins in EX-EVs were identified as non-secreted proteins. Both CAT and HIIT play common roles in neuronal signal transduction, autophagy, and cell fate regulation. Specifically, CAT showed distinct roles in cognitive function and substrate metabolism, while HIIT was more associated with organ growth, cardiac muscle function, and insulin signaling pathways. Interestingly, the miR-379 cluster within EX-EVs was specifically regulated by HIIT, involving several biological functions, including neuroactive ligand-receptor interaction. Furthermore, EX-EVs likely originate from various tissues, including metabolic tissues, the immune system, and the nervous system. Our study provides molecular insights into the effects of CAT and HIIT, shedding light on the roles of EX-EVs in mediating organ crosstalk and health promotion.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11818269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407661","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
Sterol Regulatory Element-Binding Protein Sre1 Mediates the Development and Pathogenicity of the Grey Mould Fungus Botrytis cinerea.
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2025-02-06 DOI: 10.3390/ijms26031365
Ye Yuan, Shengnan Cao, Jiao Sun, Jie Hou, Mingzhe Zhang, Qingming Qin, Guihua Li
{"title":"Sterol Regulatory Element-Binding Protein Sre1 Mediates the Development and Pathogenicity of the Grey Mould Fungus <i>Botrytis cinerea</i>.","authors":"Ye Yuan, Shengnan Cao, Jiao Sun, Jie Hou, Mingzhe Zhang, Qingming Qin, Guihua Li","doi":"10.3390/ijms26031365","DOIUrl":"10.3390/ijms26031365","url":null,"abstract":"<p><p>The grey mould fungus <i>Botrytis cinerea</i> is a dangerous plant pathogen responsible for substantial agricultural losses worldwide. The pathogenic mechanisms still have many unclear aspects, and numerous new pathogenic genes remain to be identified. Here, we show that the sterol regulatory element-binding protein Sre1 plays an important role in the development and pathogenicity of <i>B. cinerea</i>. We identified a homologue of gene <i>SRE1</i> in the <i>B. cinerea</i> genome and utilized a reverse genetics approach to create the knockout mutant Δ<i>sre1</i>. Our results demonstrate that <i>SRE1</i> is essential for conidiation, as Δ<i>sre1</i> produced only 3% of the conidia compared to the wild-type strain. Conversely, Δ<i>sre1</i> exhibited increased sclerotium production, indicating a negative regulatory role of <i>SRE1</i> in sclerotium formation. Furthermore, ergosterol biosynthesis was significantly reduced in the Δ<i>sre1</i> mutant, correlating with increased sensitivity to low-oxygen conditions. Pathogenicity assays revealed that Δ<i>sre1</i> had significantly reduced virulence, although it maintained normal infection cushion formation and penetration capabilities. Additionally, <i>SRE1</i> was found to be crucial for hypoxia adaptation, as Δ<i>sre1</i> showed abnormal germination and reduced growth under low-oxygen conditions. These findings suggest that <i>SRE1</i> mediates the development and pathogenicity of <i>B. cinerea</i> by regulating lipid homeostasis and facilitating adaptation to host tissue environments.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11818819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407811","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
Discovery of TRPV4-Targeting Small Molecules with Anti-Influenza Effects Through Machine Learning and Experimental Validation.
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2025-02-06 DOI: 10.3390/ijms26031381
Yan Sun, Jiajing Wu, Beilei Shen, Hengzheng Yang, Huizi Cui, Weiwei Han, Rongbo Luo, Shijun Zhang, He Li, Bingshuo Qian, Lingjun Fan, Junkui Zhang, Tiecheng Wang, Xianzhu Xia, Fang Yan, Yuwei Gao
{"title":"Discovery of TRPV4-Targeting Small Molecules with Anti-Influenza Effects Through Machine Learning and Experimental Validation.","authors":"Yan Sun, Jiajing Wu, Beilei Shen, Hengzheng Yang, Huizi Cui, Weiwei Han, Rongbo Luo, Shijun Zhang, He Li, Bingshuo Qian, Lingjun Fan, Junkui Zhang, Tiecheng Wang, Xianzhu Xia, Fang Yan, Yuwei Gao","doi":"10.3390/ijms26031381","DOIUrl":"10.3390/ijms26031381","url":null,"abstract":"<p><p>Transient receptor potential vanilloid 4 (TRPV4) is a calcium-permeable cation channel critical for maintaining intracellular Ca<sup>2+</sup> homeostasis and is essential in regulating immune responses, metabolic processes, and signal transduction. Recent studies have shown that TRPV4 activation enhances influenza A virus infection, promoting viral replication and transmission. However, there has been limited exploration of antiviral drugs targeting the TRPV4 channel. In this study, we developed the first machine learning model specifically designed to predict TRPV4 inhibitory small molecules, providing a novel approach for rapidly identifying repurposed drugs with potential antiviral effects. Our approach integrated machine learning, virtual screening, data analysis, and experimental validation to efficiently screen and evaluate candidate molecules. For high-throughput virtual screening, we employed computational methods to screen open-source molecular databases targeting the TRPV4 receptor protein. The virtual screening results were ranked based on predicted scores from our optimized model and binding energy, allowing us to prioritize potential inhibitors. Fifteen small-molecule drugs were selected for further in vitro and in vivo antiviral testing against influenza. Notably, glecaprevir and everolimus demonstrated significant inhibitory effects on the influenza virus, markedly improving survival rates in influenza-infected mice (protection rates of 80% and 100%, respectively). We also validated the mechanisms by which these drugs interact with the TRPV4 channel. In summary, our study presents the first predictive model for identifying TRPV4 inhibitors, underscoring TRPV4 inhibition as a promising strategy for antiviral drug development against influenza. This pioneering approach lays the groundwork for future clinical research targeting the TRPV4 channel in antiviral therapies.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11818416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407669","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 African-Specific ACE2 Polymorphisms on Omicron BA.4/5 RBD Binding and Allosteric Communication Within the ACE2-RBD Protein Complex.
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2025-02-06 DOI: 10.3390/ijms26031367
Victor Barozi, Özlem Tastan Bishop
{"title":"Impact of African-Specific ACE2 Polymorphisms on Omicron BA.4/5 RBD Binding and Allosteric Communication Within the ACE2-RBD Protein Complex.","authors":"Victor Barozi, Özlem Tastan Bishop","doi":"10.3390/ijms26031367","DOIUrl":"10.3390/ijms26031367","url":null,"abstract":"<p><p>Severe acute respiratory symptom coronavirus 2 (SARS-CoV-2) infection occurs via the attachment of the spike (S) protein's receptor binding domain (RBD) to human ACE2 (hACE2). Natural polymorphisms in hACE2, particularly at the interface, may alter RBD-hACE2 interactions, potentially affecting viral infectivity across populations. This study identified the effects of six naturally occurring hACE2 polymorphisms with high allele frequency in the African population (S19P, K26R, M82I, K341R, N546D and D597Q) on the interaction with the S protein RBD of the BA.4/5 Omicron sub-lineage through post-molecular dynamics (MD), inter-protein interaction and dynamic residue network (DRN) analyses. Inter-protein interaction analysis suggested that the K26R variation, with the highest interactions, aligns with reports of enhanced RBD binding and increased SARS-CoV-2 susceptibility. Conversely, S19P, showing the fewest interactions and largest inter-protein distances, agrees with studies indicating it hinders RBD binding. The hACE2 M82I substitution destabilized RBD-hACE2 interactions, reducing contact frequency from 92 (WT) to 27. The K341R hACE2 variant, located distally, had allosteric effects that increased RBD-hACE2 contacts compared to WThACE2. This polymorphism has been linked to enhanced affinity for Alpha, Beta and Delta lineages. DRN analyses revealed that hACE2 polymorphisms may alter the interaction networks, especially in key residues involved in enzyme activity and RBD binding. Notably, S19P may weaken hACE2-RBD interactions, while M82I showed reduced centrality of zinc and chloride-coordinating residues, hinting at impaired communication pathways. Overall, our findings show that hACE2 polymorphisms affect S BA.4/5 RBD stability and modulate spike RBD-hACE2 interactions, potentially influencing SARS-CoV-2 infectivity-key insights for vaccine and therapeutic development.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11818624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407296","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
Role of 11β-Hydroxysteroid Dehydrogenase and Mineralocorticoid Receptor on Alzheimer's Disease Onset: A Systematic Review.
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2025-02-06 DOI: 10.3390/ijms26031357
Mariangela Di Vincenzo, Pamela Pellegrino, Genny Schiappa, Anna Campanati, Valerio Del Vescovo, Silvia Piccirillo, Patrizia Ambrogini, Giorgio Arnaldi, Monia Orciani
{"title":"Role of 11β-Hydroxysteroid Dehydrogenase and Mineralocorticoid Receptor on Alzheimer's Disease Onset: A Systematic Review.","authors":"Mariangela Di Vincenzo, Pamela Pellegrino, Genny Schiappa, Anna Campanati, Valerio Del Vescovo, Silvia Piccirillo, Patrizia Ambrogini, Giorgio Arnaldi, Monia Orciani","doi":"10.3390/ijms26031357","DOIUrl":"10.3390/ijms26031357","url":null,"abstract":"<p><p>The role of 11β-HSD1 in Alzheimer's disease (AD) has garnered significant attention due to its involvement in glucocorticoid metabolism, neuroinflammation, and cognitive decline. This review explores the current understanding of 11β-HSD1 in AD, examining genetic, preclinical, and clinical research. Genetic studies have identified 11β-HSD1 polymorphisms that may influence AD risk, although findings remain inconsistent. Mechanistically, 11β-HSD1 promotes neurodegeneration through the dysregulation of glucocorticoid activity, contributing to hippocampal atrophy, amyloid plaque formation, and tau pathology. Preclinical studies have shown that 11β-HSD1 inhibitors offer neuroprotective effects, including enhanced cognitive function, reduced inflammation, and improved mitochondrial activity. However, clinical trials, including those involving ABT-384 and Xanamem, have produced mixed results, with no substantial cognitive improvements despite effective enzyme inhibition. These inconsistencies highlight the complexity of AD and the challenges in translating preclinical findings into clinical outcomes. Moreover, while 11β-HSD1 inhibition holds therapeutic potential, other strategies targeting neuroinflammation, autophagy, and glucocorticoid signaling are also being explored. Ongoing research is focusing on optimizing 11β-HSD1 inhibitors, identifying biomarkers for patient selection, and investigating combination therapies to enhance treatment efficacy. Ultimately, 11β-HSD1's role in AD presents a promising therapeutic target, but further studies are required to fully understand its potential in managing the disease.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11818399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407624","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
Adsorption of Serum Fetuin onto Octacalcium Phosphate and Its Relation to Osteogenic Property.
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2025-02-06 DOI: 10.3390/ijms26031391
Yuki Tsuboi, Ryo Hamai, Kyosuke Okuyama, Kaori Tsuchiya, Yukari Shiwaku, Kensuke Yamauchi, Osamu Suzuki
{"title":"Adsorption of Serum Fetuin onto Octacalcium Phosphate and Its Relation to Osteogenic Property.","authors":"Yuki Tsuboi, Ryo Hamai, Kyosuke Okuyama, Kaori Tsuchiya, Yukari Shiwaku, Kensuke Yamauchi, Osamu Suzuki","doi":"10.3390/ijms26031391","DOIUrl":"10.3390/ijms26031391","url":null,"abstract":"<p><p>This study aimed to investigate how the chemical elements in relation to octacalcium phosphate (OCP) hydrolysis affect the osteoblastic differentiation in the presence of serum fetuin. The adsorption of fetuin onto OCP was examined in buffers having different degrees of supersaturation (DS) with respect to OCP and hydroxyapatite (HA) at pH 7.4 and 37 °C. The osteoblastic differentiation of mesenchymal stem cells (MSCs) was evaluated in cultures with OCP and 0 to 0.8 mg/mL of fetuin. The amount of fetuin adsorbed increased with increasing DS in the buffer. In the MSC culture, the coexistence of OCP and 0.2-0.4 mg/mL of fetuin close to serum level increased alkaline phosphatase activity; however, the activity was suppressed by 0.2-0.8 mg/mL of fetuin. Transmission electron microscopy revealed de novo crystal formation on OCP in supersaturated buffer and culture media with respect to OCP and HA at lower fetuin concentrations. Infrared spectroscopy and DS estimation indicate that the hydrolysis of OCP with de novo apatite formation was promoted in the culture media at 0.2-0.4 mg/mL of fetuin. These results suggest that OCP may promote osteoblastic differentiation if the suitable conditions are attained regarding the chemical elements and fetuin adsorption around OCP.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11818475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407489","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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