International Journal of Molecular Sciences最新文献

{"title":"Special Issue \"Molecular Research in Breast Cancer: Pathophysiology and Treatment\".","authors":"Costa Frangou","doi":"10.3390/ijms26199732","DOIUrl":"10.3390/ijms26199732","url":null,"abstract":"<p><p>Breast cancer remains the most commonly diagnosed malignancy in women and a leading cause of cancer-related mortality worldwide [...].</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atherosclerotic Plaque Crystals Induce Endothelial Dysfunction.","authors":"Jishamol Thazhathveettil, Sherin Aloysius Gomez, Deborah Olaoseeji, Rongrong Wu, Allan Sirsjö, Geena Varghese Paramel","doi":"10.3390/ijms26199758","DOIUrl":"10.3390/ijms26199758","url":null,"abstract":"<p><p>Endothelial dysfunction is an early driver of atherosclerosis, yet the direct impact of endogenous crystals such as cholesterol crystals and monosodium urate on endothelial activation remains incompletely understood. In this study, we examine how crystalline stimuli modulate human umbilical vein endothelial cells by assessing inflammatory signaling, mitochondrial respiration, and neutrophil recruitment. Using dose- and time-controlled experiments, we show that CC and MSU are internalized by endothelial cells, activating NF-κB and STAT3 signaling pathways and inducing a robust pro-inflammatory cytokine profile. Notably, CC caused marked mitochondrial dysfunction, evidenced by impaired respiratory capacity and loss of membrane potential, revealing a novel bioenergetic vulnerability in endothelial cells. Both direct crystal stimulation and exposure to crystal-primed conditioned media triggered endothelial adhesion molecule expression and promoted neutrophil adhesion, indicating that soluble mediators released upon crystal stimulation can propagate vascular inflammation. These findings demonstrate that crystalline stimuli are potent vascular danger signals capable of driving endothelial inflammation, mitochondrial impairment, and immune cell engagement, which are hallmarks of early atherogenesis. By elucidating these multifaceted endothelial responses, this study provides important mechanistic insights into how crystal-induced signals may contribute to vascular dysfunction and the early stages of atherogenesis.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145299849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammation-Based Cell Ratios Beyond White Blood Cell Count for Predicting Postimplantation Syndrome After EVAR and TEVAR.","authors":"Ebubekir Sönmez, İzatullah Jalalzai, Ümit Arslan","doi":"10.3390/ijms26199753","DOIUrl":"10.3390/ijms26199753","url":null,"abstract":"<p><p>Postimplantation syndrome (PIS) is an early inflammatory response following endovascular stent-graft implantation (EVAR and TEVAR), defined by culture-negative fever and leukocytosis. The patient's preoperative inflammatory status is thought to play a central role in its development. This study aimed to evaluate whether the systemic inflammatory response index (SIRI) and the eosinophil-to-lymphocyte ratio (ELR) can serve as preoperative predictors of PIS. Clinical data from 300 patients who underwent aortic endograft implantation and laboratory results obtained 24 h before the procedure, and at 24 h, 72 h, and 1 week postoperatively, were prospectively recorded. PIS was defined as culture-negative fever ≥ 37.8 °C accompanied by leukocytosis ≥ 12,000/µL. Inflammation-based indices derived from complete blood count (SIRI and ELR), along with serum C-reactive protein (CRP) and albumin levels, were compared between patients with and without PIS. Logistic regression and receiver operating characteristic (ROC) analyses were performed to identify independent predictors. PIS developed in 55 patients (18.3%). Patients with PIS were younger (70.1 ± 8.6 vs. 72.7 ± 7.3 years; <i>p</i> = 0.042) and had larger aneurysm diameters and greater mural thrombus thickness. Preoperatively, leukocyte count, SIRI, and CRP levels were significantly higher in patients who developed PIS, whereas ELR and albumin levels were lower. Multivariable analysis showed that a larger aneurysm diameter (OR: 1.2; 95% CI: 1.0-1.3; <i>p</i> = 0.003), greater mural thrombus thickness (OR: 1.3; 95% CI: 1.0-1.6; <i>p</i> = 0.012), EVAR procedure (OR: 3.7; 95% CI: 1.2-6.3; <i>p</i> = 0.033), elevated SIRI (OR: 1.9; 95% CI: 1.2-3.1; <i>p</i> = 0.005), and higher CRP (OR: 1.4; 95% CI: 1.1-3.2; <i>p</i> = 0.003) were significantly associated with PIS. In contrast, increasing age, higher ELR, and higher albumin levels were associated with a reduced risk of PIS. Simple biomarkers routinely obtained from standard laboratory tests can contribute meaningfully to the preoperative prediction and postoperative identification of PIS. Their integration into risk stratification models and confirmation against definitive diagnostic criteria will require validation in larger, multicenter studies.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Diabetes to Degenerative Diseases: The Multifaceted Action of Metformin.","authors":"Lucrezia Irene Maria Campagnoli, Angelica Varesi, Foroogh Fahmideh, Reza Hakimizad, Petra Petkovic, Annalisa Barbieri, Nicoletta Marchesi, Alessia Pascale","doi":"10.3390/ijms26199748","DOIUrl":"10.3390/ijms26199748","url":null,"abstract":"<p><p>Metformin, an oral antihyperglycemic drug, represents the cornerstone of pharmacological treatment for type 2 diabetes mellitus (T2DM). Its primary glucose-lowering effects are well established, predominantly mediated through the activation of AMP-activated protein kinase (AMPK). This activation leads to a reduction in hepatic glucose production (primarily by inhibiting gluconeogenesis and glycogenolysis) and an increase in peripheral glucose uptake and utilization. Beyond its direct impact on glucose metabolism, metformin also improves insulin sensitivity and has beneficial effects on lipid profiles. Increasingly, research shows that metformin has pleiotropic effects. In addition to its recognized antihyperglycemic action, metformin is emerging as a regulator of cellular processes implicated in aging. Indeed, emerging evidence suggests a potential role of metformin in modulating pathways associated with longevity and ameliorating the symptoms of age-related diseases, including neurodegenerative disorders (such as Alzheimer's and Parkinson's diseases), cardiovascular diseases, age-related macular degeneration, and osteoporosis. The proposed mechanisms for these broader effects involve AMPK activation, modulation of the mTOR pathway, reduction of oxidative stress, and promotion of autophagy. After exploring the established role of metformin in T2D, this review provides a comprehensive investigation of its promising applications in the context of age-related diseases, offering valuable insights into its multifaceted therapeutic potential beyond glycemic control.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutation of the GDP-Fucose Biosynthesis Gene <i>gmds</i> Increases Hair Cell Number and Neuromast Regenerative Capacity in Zebrafish.","authors":"Muhammad T Ameen, Gerissa Fowler, Curtis R French","doi":"10.3390/ijms26199737","DOIUrl":"10.3390/ijms26199737","url":null,"abstract":"<p><p>Hearing loss affects millions and is often caused by irreversible damage to mechanosensory hair cells. Humans and other mammals lack the capacity to regenerate damaged hair cells; however zebrafish, <i>Danio rerio</i>, can regenerate hair cells that are present in the ear and mechanosensory neuromasts, making this animal an ideal model for understanding hair cell regenerative mechanisms. This study investigates the role of the GDP-fucose biosynthesis gene <i>GDP-mannose 4,6-dehydratase</i> (<i>gmds</i>) in regulating neuromast hair cell regeneration in zebrafish. Fucosylation is required for Notch signalling, a critical negative regulator of hair cell regeneration, and we therefore hypothesized that loss of <i>gmds</i> function would enhance hair cell regeneration. We demonstrate increased hair cell number in <i>gmds</i> mutants, and increased hair cell number following chemical ablation of hair cells with neomycin. Additionally, <i>gmds</i> mutants exhibited accelerated neuromast and hair cell regeneration, achieving complete restoration faster than wild-type siblings. Pharmacological inhibition of Notch signalling further enhanced hair cell regeneration in wild-type siblings but less so in <i>gmds</i> mutants, indicating that Notch signalling may partially regulate hair cell regeneration downstream of <i>gmds</i>. These findings highlight the importance of GDP-fucose biosynthesis in regulating hair cell number and regeneration, likely partially dependent on Notch signalling.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of <i>Escherichia coli</i> Autotransporters in Urinary Tract Infections and Urosepsis.","authors":"Beata Krawczyk, Paweł Wityk","doi":"10.3390/ijms26199760","DOIUrl":"10.3390/ijms26199760","url":null,"abstract":"<p><p>Urinary tract infections (UTIs) caused by Uropathogenic <i>Escherichia coli</i> (UPEC) strains are among the most common bacterial infections in humans, causing cystitis, pyelonephritis and, in the absence of appropriate treatment, sepsis. Effective therapies and preventive strategies are still lacking, which highlights the need to better understand UPEC virulence mechanisms. Herein, we describe the role of three groups of bacterial autotransporters (ATs): serine protease autotransporter (SPATE), trimeric autotransporter adhesins (TAA), and autotransporter adhesin AIDA-I, and their possible contribution to the induction of UTI and urosepsis. AT, depending on the type, exhibits functions such as adhesion, serum resistance, hemagglutination, protease activity, biofilm formation and toxin activity. By summarizing the molecular functions of AT proteins, our review highlights their potential as targets for novel therapeutic and preventive approaches against UTIs and urosepsis.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenges in Polyglutamine Diseases: From Dysfunctional Neuronal Circuitries to Neuron-Specific CAG Repeat Instability.","authors":"Roxana Deleanu","doi":"10.3390/ijms26199755","DOIUrl":"10.3390/ijms26199755","url":null,"abstract":"<p><p>Several genetic diseases affecting the human nervous system are incurable and insufficiently understood. Among them, nine rare diseases form the polyglutamine (polyQ) family: Huntington's disease (HD), spinocerebellar ataxia types 1, 2, 3, 6, 7, and 17, dentatorubral pallidoluysian atrophy, and spinal and bulbar muscular atrophy. In most patients, these diseases progress over decades to cause severe movement incoordination and neurodegeneration. Although their inherited genes with tandem-repeat elongations and the encoded polyQ-containing proteins have been extensively studied, the neuronal-type-specific pathologies and their long pre-symptomatic latency await further investigations. However, recent advances in detecting the single-nucleus transcriptome, alongside the length of tandem repeats in HD post-mortem brains, have enabled the identification of very high CAG repeat sizes that trigger transcriptional dysregulation and cell death in specific projection neurons. One challenge is to better understand the complexity of movement coordination circuits, including the basal ganglia and cerebellum neurons, which are most vulnerable to the high CAG expansion in each disease. Another challenge is to detect dynamic changes in CAG repeat length and their effects in vulnerable neurons at single-cell resolution. This will offer a platform for identifying pathological events in vulnerable long projection neurons and developing targeted therapies for all tandem-repeat expansions affecting the CNS projection neurons.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurofilament Biomarkers in Neurology: From Neuroinflammation to Neurodegeneration, Bridging Established and Novel Analytical Advances with Clinical Practice.","authors":"Ariadne Daponte, Christos Koros, Charalampos Skarlis, Daphne Siozios, Michail Rentzos, Sokratis G Papageorgiou, Maria Anagnostouli","doi":"10.3390/ijms26199739","DOIUrl":"10.3390/ijms26199739","url":null,"abstract":"<p><p>Neuroaxonal damage underlies permanent disability in various neurological conditions, both neuroautoimmune and neurodegenerative. It is crucial to accurately quantify and monitor axonal injury using biomarkers to evaluate disease progression and treatment effectiveness and offer prognostic insights. Neurofilaments (NFs), and especially neurofilament light chain (NfL), show promise for this purpose, as their levels increase with neuroaxonal damage in both cerebrospinal fluid and blood, independent of specific causal pathways. Recent advances in ultrasensitive immunoassays enable the reliable detection of NFs in blood, transforming them from research tools into clinically applicable measures. In multiple sclerosis (MS), serum NfL correlates with disease activity, treatment response, and long-term disability, and may complement MRI in monitoring subclinical progression. In MS, NfL is primarily emerging as a marker of disease activity and treatment response; in amyotrophic lateral sclerosis (ALS), it has progressed further, being integrated into clinical trials as a pharmacodynamic endpoint and considered by regulatory agencies as a drug development tool. Additionally, NFs are increasingly being investigated in Alzheimer's disease, frontotemporal dementia, and other neurodegenerative disorders, though their disease specificity is limited. Ongoing challenges include older and novel assay harmonization, normative range interpretation, biological and analytical variability, and integration with other molecular and imaging biomarkers. This critical narrative review synthesizes the existing literature on NFs as diagnostic, prognostic, predictive, and pharmacodynamic biomarkers and discusses their role in therapeutic development and precision medicine in neuroautoimmune and neurodegenerative diseases.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single Nucleotide Polymorphisms in Oxidative Stress-Related Genes Are Associated with Autism Spectrum Disorders.","authors":"Giulia Spoto, Maria Paola Bertuccio, Giuseppa Visalli, Monica Currò, Gabriella Di Rosa, Daniela Caccamo","doi":"10.3390/ijms26199768","DOIUrl":"10.3390/ijms26199768","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) is a complex group of severe neurodevelopmental disorders characterized by varying degrees of dysfunctional communication and social abilities as well as repetitive and compulsive stereotypic behaviors. We aim to evaluate the genetic predisposition to oxidative response and its relationship with altered oxidative stress markers in ASD patients. Genomic DNA was isolated from peripheral blood lymphocytes of 106 (83 M, 23 F; 7.9 ± 3.2 years) ASD patients and 90 healthy subjects (63 M, 27 F; 21.2 ± 1.8 years). Genotyping was performed by real-time PCR-based allelic discrimination, PCR and electrophoresis of GST deletion variants. Reactive oxygen metabolites (dROMs), the Biological Antioxidant Potential (BAP), and the advanced oxidation protein products (AOPP) were also measured. Furthermore, we assessed oxidative DNA damage by Single Cell Gel Electrophoresis. The evaluation of oxidative stress markers indicated a mild oxidative stress status and a higher level of DNA damage in nuclei of ASD patients' lymphocytes. We found significant associations between ASD and several polymorphisms of genes involved in the detoxification and the response to oxidative stress. Genetic and environmental factors contribute to the onset of autism spectrum disorder, and ASD patients' treatment requires a multimodal approach, including behavioral, educational, and pharmacological approaches.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Maternal Overweight and Obesity on Adipokines During Pregnancy and Lactation.","authors":"Anita Froń, Paulina Tomecka, Magdalena Orczyk-Pawiłowicz","doi":"10.3390/ijms26199757","DOIUrl":"10.3390/ijms26199757","url":null,"abstract":"<p><p>Maternal overweight and obesity have reached global epidemic levels, altering metabolic adaptations during pregnancy and lactation. Beyond their well-known impact on gestational outcomes, elevated BMI profoundly influences the secretion of adipokines-hormones derived from adipose tissue that circulate in maternal blood and are secreted into breast milk-thereby directly linking maternal metabolism to offspring development. In this state-of-the-art narrative review, we synthesize current evidence on how maternal overweight and obesity shape concentrations of key adipokines (leptin, adiponectin, ghrelin, obestatin, and resistin) in serum, cord blood and breast milk. Excess maternal weight robustly increases leptin, while effects on adiponectin, ghrelin, obestatin, and resistin remain uncertain. To our knowledge, this is the first review to focus specifically on the impact of maternal overweight and obesity on adipokine alterations across both pregnancy and lactation. Future studies should apply standardized sampling and analytical protocols and use longitudinal designs including body composition assessments to clarify their role in maternal and child metabolic health.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145299905","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}