Ana Nava-Ochoa, Susanne U Mertens-Talcott, Stephen T Talcott, Giuliana D Noratto
{"title":"Dark Sweet Cherry (<i>Prunus avium</i> L.) Juice Phenolics Rich in Anthocyanins Exhibit Potential to Inhibit Drug Resistance Mechanisms in 4T1 Breast Cancer Cells via the Drug Metabolism Pathway.","authors":"Ana Nava-Ochoa, Susanne U Mertens-Talcott, Stephen T Talcott, Giuliana D Noratto","doi":"10.3390/cimb47030213","DOIUrl":"10.3390/cimb47030213","url":null,"abstract":"<p><p>Anthocyanins (ACNs) from dark sweet cherries (DSCs) have shown efficacy against breast cancer (BC) cells, particularly triple-negative breast cancer (TNBC) cells, without affecting normal breast cells. This study investigated the impact of ACNs on TNBC cells, focusing on drug resistance mechanisms involving drug metabolism and transport enzymes. Specifically, it was examined whether ACNs influenced Doxorubicin (DOX) metabolism by targeting drug metabolism enzymes (phase I metabolism) and drug transport enzymes (phase III metabolism) in TNBC cells. 4T1 TNBC cells were treated with ACNs, DOX, and the combination of both (ACN-DOX). Results showed a synergistic inhibition of cell viability by ACNs and DOX. In addition, the modulation of phase I drug-metabolizing enzymes was exerted by ACNs, reducing the activity of cytochrome P450 (CYP) enzymes induced by DOX. A reduction of drug efflux by ACNs was shown by decreasing P-glycoprotein (P-gp) activity, leading to a higher intracellular accumulation of DOX. These effects were confirmed using CYP and P-gp inducers and inhibitors, showing their impact on cell viability. In conclusion, the combination of ACNs with DOX has the potential to lower DOX doses, enhance its efficacy, and possibly reduce side effects, offering a promising approach for TNBC treatment.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11941269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sarah Adriana Scuderi, Alessio Ardizzone, Emanuela Esposito, Anna Paola Capra
{"title":"ABCB1-Mediated Colchicine Transport and Its Implications in Familial Mediterranean Fever: A Systematic Review.","authors":"Sarah Adriana Scuderi, Alessio Ardizzone, Emanuela Esposito, Anna Paola Capra","doi":"10.3390/cimb47030210","DOIUrl":"10.3390/cimb47030210","url":null,"abstract":"<p><p>Familial Mediterranean fever (FMF) is an autoinflammatory genetic disorder characterized by recurrent fevers and inflammation of the serous membranes in the abdomen, lungs, and joints. Currently, the standard treatment of FMF includes colchicine, which is an alkaloid, derived from <i>Colchicum autumnale</i>. Colchicine's efficacy in FMF is well-established as it is used both to prevent acute attacks and reduce the risk of long-term complications. However, despite these available treatments, 5-10% of patients exhibit resistance to the drug. It has been demonstrated that polymorphisms in several genes involved in inflammation can influence treatment outcomes and the risk of FMF complications like amyloidosis. Among them, some research focused on polymorphism affecting adenosine triphosphate (ATP)-binding cassette sub-family B member 1 (<i>ABCB1</i>) gene encoding for P-glycoprotein. P-glycoprotein is considered a key transporter protein as it regulates the absorption, distribution, and excretion of several drugs, including colchicine. In diseases like FMF, <i>ABCB1</i> polymorphisms have been shown to affect the response to colchicine, potentially leading to treatment resistance or altered toxicity. Based on this evidence, this systematic review aims to analyze available evidence on ABCB1-mediated colchicine transport and its clinical implications in FMF, showing how relevant <i>ABCB1</i> variants are in response to therapy.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11941201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"USP5 Suppresses Ferroptosis in Bladder Cancer Through Stabilization of GPX4.","authors":"Caiying Liu, Yanong Deng, Liang Huang, Xinrui Nie, Yuxuan Jiang, Xia Zhang, Huihui Zhang","doi":"10.3390/cimb47030211","DOIUrl":"10.3390/cimb47030211","url":null,"abstract":"<p><p>USP5 has been proven to play an important role in the proliferation of bladder cancer (BC). In this study, we focused on investigating the molecular mechanism of ferroptosis induced by USP5 in bladder cancer. The role of USP5 in bladder cancer was evaluated using T24 wild-type cells (WT) and USP5 knockout (USP5<sup>-/-</sup>) by CCK8 and colony formation assays. The contents of ferrobivalent ions (Fe<sup>2+</sup>), reactive oxygen species (ROS), and malondialdehyde (MDA) were detected using a determination kit to observe the relationship between USP5 and ferroptosis. Furthermore, the molecular mechanism study was evaluated by employing Western blotting, co-immunoprecipitation, RT-qPCR, ubiquitination assays, etc. This study showed genetic ablation of USP5 significantly inhibited the viability and proliferation of bladder cancer cells. Genetic ablation of USP5 promoted increases in Fe<sup>2+</sup> content, ROS, and MDA levels. The addition of erastin significantly increased the viability and proliferation of T24 USP5<sup>-/-</sup> cells and significantly increased their ROS and MDA contents. We verified that USP5 deficiency led to a significant reduction in GPX4 protein levels and that the overexpression of USP5 could stabilize the GPX4 protein. Further studies showed that USP5 interacts with GPX4 and stabilizes GPX4 by inhibiting its ubiquitination These findings revealed USP5 inhibits ferroptosis in bladder cancer cells by stabilizing GPX4. The relationship between USP5 and ferroptosis could be a potential therapeutic target for bladder cancer.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11941033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vito Spagnuolo, Marco Piergentili, Ilaria Passerini, Vittoria Murro, Dario Pasquale Mucciolo, Dario Giorgio, Martina Maccari, Elisabetta Pelo, Ilaria Biagini, Fabrizio Giansanti, Gianni Virgili, Andrea Sodi
{"title":"Retinal Dystrophies Associated with Mutations in the <i>RP1</i> Gene: Genotype-Phenotype Correlations.","authors":"Vito Spagnuolo, Marco Piergentili, Ilaria Passerini, Vittoria Murro, Dario Pasquale Mucciolo, Dario Giorgio, Martina Maccari, Elisabetta Pelo, Ilaria Biagini, Fabrizio Giansanti, Gianni Virgili, Andrea Sodi","doi":"10.3390/cimb47030212","DOIUrl":"10.3390/cimb47030212","url":null,"abstract":"<p><strong>Background: </strong>We evaluated the genetic and phenotypic features of a cohort of 10 Italian patients affected by Retinitis Pigmentosa (RP) associated with <i>RP1</i> sequence variants.</p><p><strong>Methods: </strong>A retrospective, cross-sectional genotype-phenotype correlation study was conducted on a cohort of ten Italian patients (four males and six females) seen at Careggi University Hospital between 2012 and 2024, all affected by RP carrying pathogenic variants in the RP1 gene. A comprehensive ophthalmic assessment and pedigree analysis were performed, focusing on the onset of disease symptoms, the patient's age at first diagnosis, follow-up duration, and the presence of comorbidities.</p><p><strong>Results: </strong>Our cohort included ten Italian patients with a mean age of 59 (range of 32-79 years). The median age when symptoms first presented was 43 years (range of 2-74), with a mean follow-up period of 9.3 ± 2.6 years. The main symptoms at presentation were hemeralopia and visual field constriction. Fundus examination revealed a classic RP phenotype. Fundus autofluorescence (FAF), optical coherence tomography (OCT), Electroretinogram (ERG), and visual field testing confirmed the typical features of classic retinitis pigmentosa in most cases.</p><p><strong>Conclusions: </strong>This single-center cohort of Italian patients provides insights into the clinical and genetic characteristics of <i>RP1</i>-associated RP. By comprehensively identifying genetic variations and their associated clinical manifestations, therapeutic interventions targeting specific genetic abnormalities can be better tailored. This approach holds promise for improving the prognosis and quality of life for individuals with <i>RP1</i>-associated RP.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11941481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaowu Sun, Guangli Shi, Songze Li, Jun Ai, Dan Sun, Zhenxing Wang, Peijin Ni, Zhendong Zhang, Shuaiming Chen, Zelong Du, Xiang Li, Fan Zhang
{"title":"Genetic Diversity of a Wild <i>Actinidia arguta</i> Population in Changbai Mountain Determined by Simple Sequence Repeat Markers.","authors":"Xiaowu Sun, Guangli Shi, Songze Li, Jun Ai, Dan Sun, Zhenxing Wang, Peijin Ni, Zhendong Zhang, Shuaiming Chen, Zelong Du, Xiang Li, Fan Zhang","doi":"10.3390/cimb47030207","DOIUrl":"10.3390/cimb47030207","url":null,"abstract":"<p><p>With the decrease in the number of natural populations of <i>Actinidia arguta</i>, there is an urgent need to collect <i>A. arguta</i> germplasm resources and explore their genetic diversity for better management and protection. In this study, 31 simple sequence repeat (SSR) markers were used to identify 148 wild <i>A. arguta</i> germplasms from six natural populations in Changbai Mountain, China, and the genetic diversity of their leaf quality traits was subsequently evaluated. SSR analysis revealed rich genetic diversity among different individuals and within populations of <i>A. arguta</i>. Molecular variance analysis determined that the genetic diversity of wild <i>A. arguta</i> mainly came from within the populations (95% variance component ratio), while only a small part originated from among populations (5% variance component ratio). Abundant genetic variations were observed in the leaf quality traits of the different <i>A. arguta</i> resources with a high genetic diversity index (0.13-1.23). Leaf quality trait clustering and the unweighted pair group method with arithmetic average (UPGMA) clustering analysis showed similar classification results. Population structure analysis divided 148 individuals into three subgroups. Our results indicate that the populations of <i>A. arguta</i> in Changbai Mountain have large genetic variation and high genetic diversity. This study broadens the genetic basis of the <i>A. arguta</i> breeding germplasm.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mengxuan Sun, Yang Yu, Hanci Zhu, Yan Yao, Xintong Zhou, Xue Wang, Yubao Zhang, Xiaowei Xu, Jing Zhuang, Changgang Sun
{"title":"Hepatic Growth Factor as a Potential Biomarker for Lung Adenocarcinoma: A Multimodal Study.","authors":"Mengxuan Sun, Yang Yu, Hanci Zhu, Yan Yao, Xintong Zhou, Xue Wang, Yubao Zhang, Xiaowei Xu, Jing Zhuang, Changgang Sun","doi":"10.3390/cimb47030208","DOIUrl":"10.3390/cimb47030208","url":null,"abstract":"<p><p>(1) Background: Despite previous studies linking inflammatory cytokines to lung adenocarcinoma (LUAD), their causal mechanisms remain unclear. This study aims to explore the causal relationship between inflammatory cytokines and LUAD to fill this knowledge gap. (2) Methods: This study employs a comprehensive approach, integrating Mendelian randomization (MR) analysis, single-cell RNA sequencing (scRNA-seq), and transcriptomic sequencing (RNA-seq) data to investigate the relationship between inflammatory cytokines and LUAD. (3) Results: In forward MR analysis, elevated levels of hepatocyte growth factor (HGF), interleukin-1 receptor antagonist (IL-1RA), IL-5, monocyte chemoattractant protein-3, and monokine induced by interferon-γ were causally associated with an increased risk of LUAD. In reverse MR analysis, LUAD exhibited a positive causal relationship with the levels of regulated upon activation normal T cell expressed and secreted factor (RANTES) and stromal cell-derived factor-1α. The scRNA-seq data further identified specific cell populations that may influence LUAD onset and progression through the expression of particular inflammatory genes and intercellular communication. RNA-seq data analysis highlighted the role of the HGF gene in LUAD diagnosis, demonstrating its strong correlation with patient prognosis and immune cell infiltration within the tumor microenvironment. (4) Conclusions: The findings reveal a causal relationship between inflammatory cytokines and LUAD, with HGF emerging as a potential biomarker of significant clinical relevance. This study provides new insights into the molecular mechanisms underlying LUAD and lays the foundation for future therapeutic strategies.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11941628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Fisetin Mitigates Chronic Lung Injury Induced by Benzo(a)Pyrene by Regulation of Inflammation and Oxidative Stress.","authors":"Wanian M Alwanian","doi":"10.3390/cimb47030209","DOIUrl":"10.3390/cimb47030209","url":null,"abstract":"<p><p><b>Background</b>: Polycyclic aromatic hydrocarbons such as Benzo(a)Pyrene, which are produced by smoking or present in air pollution, greatly contribute to lung diseases. B(a)P has been found to induce inflammation and eventually lung cancer. Fisetin, a polyphenol, abundant in many fruits and vegetables, has an appealing therapeutic potential in many disorders, including inflammation and cancer. <b>Objectives</b>: This study aimed to investigate the importance of fisetin in the regulation of chronic lung inflammation and oxidative stress resulting from exposure to Benzo(a)Pyrene. <b>Methods</b>: The effect of fisetin on rats at a concentration of 50 mg/kg was evaluated by ELISA to measure oxidative stress and inflammatory markers. The tissue architecture was also investigated using hematoxylin and eosin (H&E) staining. The expression pattern of IL-6 in lung tissues was assayed using immunohistochemistry. Fibrosis was evaluated in lung tissues using Masson Trischrome and Sirius red stains. Cell apoptosis in lung tissues was studied using a TUNEL assay. <b>Results</b>: After exposure to Benzo(a)Pyrene for eight weeks, the data indicated that fisetin led to a significant reduction in oxidative stress, evidenced by the reduction of SOD, MDA, NO, GPH, and GPx. Moreover, IL-6, TNF-α, and CRP levels were also decreased, indicating a reduction in inflammation. Apoptosis was reduced upon fisetin treatment. Furthermore, a significant decrease in fibrosis was also observed. <b>Conclusions</b>: This study reveals the importance of fisetin as a natural product in the management of chronic lung injury by protecting lung tissues from inflammation, and its use suggests better prognosis in diseases caused by exposure to B(a)P.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11941139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Novel Ferroptosis-Related Gene Prognosis Signature and Identifying Atorvastatin as a Potential Therapeutic Agent for Hepatocellular Carcinoma.","authors":"Ling Wang, Xiaoqin He, Yang Shen, Jiayu Chen, Yukai Chen, Zhuolin Zhou, Ximing Xu","doi":"10.3390/cimb47030201","DOIUrl":"10.3390/cimb47030201","url":null,"abstract":"<p><p>Among the most common malignant tumors, hepatocellular carcinoma (HCC) is a primary liver cancer type that has a high mortality rate. HCC often presents insidiously, is prone to recurrence, and has limited treatment efficacy. Ferroptosis regulates tumorigenesis, progression, and metastasis, which is a novel form of iron-dependent cell death. Numerous studies suggest that HCC is sensitive to ferroptosis, indicating that targeted therapies aimed at inducing ferroptosis may represent a promising new approach to cancer treatment. This study aims to find genes associated with HCC and ferroptosis, as well as to screen for potential agents that may cause ferroptosis in HCC. Transcriptome and clinical sample data were obtained from the TCGA database to identify differentially expressed genes related to ferroptosis. Using various regression and survival analysis techniques, we developed a prognostic model based on four core genes and evaluated its predictive potential. Subsequently, we screened for potential therapeutic agents in the Connective Map (CMap) database, designated as compound Atorvastatin, based on differential genes from two risk groups and related to ferroptosis. Through experiments conducted in vivo and in vitro, we demonstrated that Atorvastatin can induce ferroptosis in HCC cells while inhibiting their growth and migration. In conclusion, this research targets ferroptosis therapy and provides new insights for improving the prediction and prevention of HCC.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Proposal for Research Involving New Biomarkers of Hypertension, Lifestyle, and Environmental Exposure.","authors":"Angelika Edyta Charkiewicz","doi":"10.3390/cimb47030206","DOIUrl":"10.3390/cimb47030206","url":null,"abstract":"<p><p>The constant monitoring of the population's diet and assessment of occupational exposure and environmental impacts are the key to determining health risks and understanding the factors contributing to potential abnormalities in developing lifestyle diseases. Extensive long-term lifestyle monitoring studies can provide data on population health risks, including the most common cardiovascular diseases like hypertension. This paper presents research recommendations for future researchers and doctors to improve the diagnosis of hypertension and targeted, personalised treatment. The research proposal includes a lifestyle study, a diagnostic panel with new biomarkers, and an environmental exposure assessment of men working in the metallurgical industry. New developments and improved interventions are constantly being sought, including new biomarkers with high diagnostic utility for cardiovascular diseases like hypertension. This should enable early diagnosis, and consequently allow for appropriate and, most importantly, personalised therapy, and prevent an increase in CVD deaths. Only the effective diagnosis, treatment, and monitoring of hypertension can reduce the risk of developing diseases associated with hypertension. I propose that several new parameters (NO, cfDNA, MPO, PCSK9, MyBPC3, microRNA, TAS, Pb, and Cd) with prognostic and/or predictive potential should be included in screening to confirm the need for the extensive testing of middle-aged men by healthcare professionals due to the risk of hypertension.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11941015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abel Isaías Gutiérrez Cruz, Guillermo de Anda-Jáuregui, Enrique Hernández-Lemus
{"title":"Gene Co-Expression Analysis Reveals Functional Differences Between Early- and Late-Onset Alzheimer's Disease.","authors":"Abel Isaías Gutiérrez Cruz, Guillermo de Anda-Jáuregui, Enrique Hernández-Lemus","doi":"10.3390/cimb47030200","DOIUrl":"10.3390/cimb47030200","url":null,"abstract":"<p><p>The rising prevalence of Alzheimer's disease (AD), particularly among older adults, has driven increased research into its underlying mechanisms and risk factors. Aging, genetic susceptibility, and cardiovascular health are recognized contributors to AD, but how the age of onset affects disease progression remains underexplored. This study investigates the role of early- versus late-onset Alzheimer's disease (EOAD and LOAD, respectively) in shaping the trajectory of cognitive decline. Leveraging data from the Religious Orders Study and Memory and Aging Project (ROSMAP), two cohorts were established: individuals with early-onset AD and those with late-onset AD. Comprehensive analyses, including differential gene expression profiling, pathway enrichment, and gene co-expression network construction, were conducted to identify distinct molecular signatures associated with each cohort. Network modularity learning algorithms were used to discern the inner structure of co-expression networks and their related functional features. Computed network descriptors provided deeper insights into the influence of age at onset on the biological progression of AD.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11941623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}