Experimental and molecular pathology最新文献

{"title":"Expression of concern: “The critical roles of lncRNAs in the pathogenesis of melanoma” [Experimental and Molecular Pathology 117 (2020) 104558]","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"145 ","pages":"Article 105019"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147449065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breaking barriers: Innovative therapies for managing homozygous familial hypercholesterolemia","authors":"Shuai-Jie Huang ,&nbsp;Ping Huang ,&nbsp;Nan-Nan Song ,&nbsp;Xian-Hui Jia ,&nbsp;Hong-Li Gao ,&nbsp;Zhi-Yuan Lu ,&nbsp;Xiao-Lan Wen","doi":"10.1016/j.yexmp.2025.105003","DOIUrl":"10.1016/j.yexmp.2025.105003","url":null,"abstract":"<div><div>Homozygous familial hypercholesterolemia (HoFH) is a rare autosomal recessive disorder characterized by variants in genes involved in the regulation of low-density lipoprotein cholesterol (LDL-C) metabolism. The genetic basis of HoFH is complex, with biallelic variants in the low-density lipoprotein receptor (<em>LDLR</em>) gene being the most prevalent. Early diagnosis and appropriate lipid-lowering therapy (LLT) are essential for patients with HoFH to prevent the premature onset of atherosclerotic cardiovascular disease (ASCVD). Effective and timely reduction of LDL-C levels is crucial for the success of LLT. Nevertheless, the majority of patients with HoFH exhibit resistance to conventional LLT due to insufficient or absent activity of LDL-R, rendering the management of HoFH challenging. Recent advancements have introduced novel pharmacological agents for treating HoFH (e.g. evolocumab, alirocumab, inclisiran and bempedoic acid), including cholesterol-lowering strategies that function independently of LDL-R such as lomitapide and evinacumab offering significant promise for managing this condition. However, disparities in the treatment of HoFH persist across different regions and countries. In this context, the review provides a comprehensive overview of established treatment modalities and emerging therapeutic agents for individuals with HoFH.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"144 ","pages":"Article 105003"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Celecoxib and naproxen disrupt autophagy and activate EGR1 in kidney tubules","authors":"Samaneh Haghighi ,&nbsp;Arezoo Haghighi ,&nbsp;Zoltán S. Zádori ,&nbsp;Krisztián Kovács ,&nbsp;Anna Manzéger ,&nbsp;Gábor Kökény","doi":"10.1016/j.yexmp.2025.105000","DOIUrl":"10.1016/j.yexmp.2025.105000","url":null,"abstract":"<div><div>Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for their analgesic effects, although the possible COX-independent impact on the kidneys is largely unknown. Kidney damage is often associated with defective autophagy and autophagy dysregulation has been associated with kidney fibrosis and the pro-fibrotic EGR1 transcription factor activation. The non-selective COX inhibitor indomethacin (IND) can be nephrotoxic, but the impact of selective COX-2 inhibitor celecoxib (CEL) or the non-selective naproxen (NAP) on renal autophagy and EGR1 remain obscure. Here, we investigated the dose-dependent effect of CEL and NAP administration on human proximal tubule epithelial (HK-2) cells and murine inner medullary collecting duct (IMCD) cells in comparison to the effects of IND. To elucidate chronic renal effects, we also treated rats similarly for two weeks. We found that high doses of CEL and NAP, but not IND, disrupted autophagy, increased oxidative stress, and activated pro-fibrotic pathways in both HK-2 and IMCD cells with induced EGR1, accompanied by ACTA2 upregulation. We found similar effects in the renal medulla of rats treated with high-dose CEL and NAP. In addition, autophagy dysfunction was evident through increased LC3-II/I and p62 accumulation. Histology confirmed dose-dependent tubular damage and nuclear EGR1 accumulation in CEL and NAP treated rats, accompanied by induced HMOX1 and AKT phosphorylation. Our study reveals dose-dependent tubulotoxic effects of NSAIDs unrelated to their COX-selectivity, suggesting an interplay between pro-fibrotic transcription factor EGR1, autophagy pathways and oxidative stress. These findings underscore the need for meticulous dose optimization especially in kidney disease patients in order to reduce nephrotoxicity.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"144 ","pages":"Article 105000"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145267323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prospective evaluation of copy number alterations validates chromosome 1q gain as an independent marker of poor prognosis in localized Ewing sarcoma","authors":"Juan Díaz-Martín ,&nbsp;Andreas Ranft ,&nbsp;Maite Blanquer-Maceiras ,&nbsp;Rosa Noguera ,&nbsp;Carmen Salguero-Aranda ,&nbsp;Daniel Delgado-Bellido ,&nbsp;Laura Romero-Pérez ,&nbsp;Uta Dirksen ,&nbsp;Enrique de Álava","doi":"10.1016/j.yexmp.2025.105008","DOIUrl":"10.1016/j.yexmp.2025.105008","url":null,"abstract":"<div><h3>Background</h3><div>Ewing sarcoma is a rare and aggressive tumor affecting mainly adolescents and young adults. Accurate risk stratification is critical for treatment tailoring, yet traditional clinical parameters lack sufficient predictive accuracy. While retrospective studies have identified potential molecular biomarkers, prospective validation is required for clinical implementation.</div></div><div><h3>Methods</h3><div>The international PROVABES consortium (PROspective Validation of Biomarkers in Ewing Sarcoma) aims to evaluate molecular prognostic markers in European patients treated under international phase III trials. This study focuses on copy number alterations (CNAs), in 305 primary tumors. Tissue microarrays were analyzed by FISH for chromosome 1q gain (<em>n</em> = 297) and 16q loss (<em>n</em> = 266). Genome-wide CNAs were further assessed using SNP arrays in 139 samples. Associations with clinical outcomes were evaluated via Kaplan-Meier and multivariate Cox regression, with event-free survival (EFS) and overall survival (OS) as endpoints.</div></div><div><h3>Results</h3><div>Chromosome 1q gain was significantly associated with shorter OS in both localized cases and the overall cohort, and with inferior EFS specifically in localized patients. In contrast, 16q loss showed no significant prognostic impact. Multivariate analysis confirmed 1q gain as an independent predictor of poor EFS in localized disease. Notably, a higher fraction of genome altered was associated with inferior OS and EFS not only in localized patients but also in the entire cohort, and remained an independent predictor of outcome despite the smaller subset analyzed.</div></div><div><h3>Conclusions</h3><div>This prospective study validates chromosome 1q gain as an independent marker of poor prognosis in localized Ewing sarcoma. Furthermore, the extent of genomic alteration emerges as a promising predictor of both OS and EFS. Incorporating these biomarkers may improve individualized risk stratification and ultimately enhance patient outcomes.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"144 ","pages":"Article 105008"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145549016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High KCNJ14 expression is associated with an immunosuppressive tumor microenvironment and advanced pathological features: An RNA in situ hybridization-based analysis of colorectal carcinoma","authors":"Hiroshi Sawaguchi ,&nbsp;Takeshi Uehara ,&nbsp;Mai Iwaya ,&nbsp;Shiho Asaka ,&nbsp;Tomoyuki Nakajima ,&nbsp;Shotaro Komamura ,&nbsp;Shunsuke Imamura ,&nbsp;Yugo Iwaya ,&nbsp;Shinsuke Sugenoya ,&nbsp;Masato Kitazawa ,&nbsp;Yuji Soejima ,&nbsp;Hiroyoshi Ota ,&nbsp;Tadanobu Nagaya","doi":"10.1016/j.yexmp.2025.105005","DOIUrl":"10.1016/j.yexmp.2025.105005","url":null,"abstract":"<div><div>Colorectal carcinoma (CRC) remains one of the leading causes of cancer-related deaths worldwide, and there is a lack of reliable biomarkers to predict tumor progression and the immune microenvironment. <em>KCNJ14</em> is a member of the inwardly rectifying potassium channel family that has recently been implicated in tumor progression and immune suppression; however, its clinical significance and spatial expression patterns in CRC remain unclear. We evaluated <em>KCNJ14</em> mRNA expression by RNA in situ hybridization using an RNAscope on a tissue microarray of 259 CRC cases. We assessed the associations between <em>KCNJ14</em> expression and clinicopathological features, tumor-infiltrating CD4⁺, CD8⁺, and FOXP3⁺ cells, and patient outcomes. We also performed single-cell RNA sequencing analysis to determine the cell type-specific expression of <em>KCNJ14</em>. <em>KCNJ14</em> expression was predominantly observed in cancer cells, with high expression identified in 36 cases. High <em>KCNJ14</em> expression was significantly associated with lymphatic invasion, venous invasion, lymph node metastasis, and advanced disease stage. High <em>KCNJ14</em> expression was also correlated with decreased intratumoral infiltration of CD4⁺ and CD8⁺ T cells, as well as lower tumor-infiltrating lymphocyte scores, indicating an immunosuppressive tumor microenvironment. In contrast, there were no significant associations between <em>KCNJ14</em> expression and FOXP3⁺ cell infiltration, overall survival, or recurrence-free survival. This study is the first to demonstrate that high <em>KCNJ14</em> expression is associated with an immunosuppressive tumor microenvironment and advanced pathological features in CRC. Although <em>KCNJ14</em> is not an independent prognostic factor, it may serve as a potential indicator of an immunosuppressive tumor microenvironment and be a novel therapeutic target.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"144 ","pages":"Article 105005"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wharton's jelly-derived nanovesicles for targeting intervertebral disc degeneration","authors":"Letizia Penolazzi ,&nbsp;Alice Zaramella ,&nbsp;Anna Chierici ,&nbsp;Paola Bisaccia ,&nbsp;Maria Pina Notarangelo ,&nbsp;Anna Maria Tolomeo ,&nbsp;Elisabetta Lambertini ,&nbsp;Anna Alessia Saponaro ,&nbsp;Tommaso Colangelo ,&nbsp;Michela Pozzobon ,&nbsp;Roberta Piva","doi":"10.1016/j.yexmp.2025.105011","DOIUrl":"10.1016/j.yexmp.2025.105011","url":null,"abstract":"<div><div>The present study was designed to characterize the matrix-bound nanovesicles (MBVs) in decellularized Wharton's jelly matrix (DWJ). We have previously used DWJ as a biomaterial demonstrating its efficacy in restoring the functional properties of human intervertebral disc (IVD) cells lost following degeneration (IDD), for which there is currently no cure.</div><div>MBVs were isolated by ultracentrifugation from DWJ, characterized by transmission electron microscopy, nanoparticle tracking assay, and surface marker expression. MBVs uptake into cells was assessed by CalceinAM labeling. Nitric oxide production was evaluated by Griess assay. The response of IVD cells was assessed by cell motility (wound scratch assay) and protein expression (immunocytochemistry). MBVs were subjected to human growth factors array to evaluate different growth factors and global miRNA profiling (obtained from miRNA libraries, sequencing-NextSeq system and the GeneGlobe Data Analysis).</div><div>MBVs were readily internalized by cells without affecting the viability. MBVs suppressed the acquisition of the M1 phenotype in LPS-stimulated macrophages, positively influence the cell migration of IVD cells and the expression of molecular markers associated with the restoration of the chondrocyte-like phenotype. A preliminary analysis of growth factor content and miRNA expression profiling suggest that MBVs carry a cargo functionally relevant for the IVD cell metabolism.</div><div>The discovery of MBVs in DWJ leads to considering them as an integral component of DWJ-based scaffolds designed to repair or regenerate a damaged tissue. The pro-discogenic properties of MBVs demonstrate that there are grounds for expanding the study of DWJ-derived MBVs for potential therapeutic applications in the treatment of IDD.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"144 ","pages":"Article 105011"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145620296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RBFOX2: An RNA-binding protein with alternative splicing and non-alternative splicing regulatory functions","authors":"Wei Wang ,&nbsp;Yang Zhang ,&nbsp;Siyi Liu ,&nbsp;Shan Liao ,&nbsp;Junyu He ,&nbsp;Gengqiu Luo ,&nbsp;Qian He ,&nbsp;Yanhong Zhou","doi":"10.1016/j.yexmp.2025.105007","DOIUrl":"10.1016/j.yexmp.2025.105007","url":null,"abstract":"<div><div>RNA-binding Fox-1 homolog 2 (RBFOX2) is a key RNA-binding protein that primarily functions by regulating alternative splicing. Furthermore, RBFOX2 regulates RNA metabolism across the transcriptional and multiple post-transcriptional stages, encompassing recognizing RNA epigenetic modifications, inhibiting transcription, regulating alternative polyadenylation, inhibiting miRNA processing, and stabilizing mRNA. Additionally, RBFOX2 is regulated by upstream factors such as RNA binding proteins, non-coding RNAs, and transcription factors. RBFOX2 is extensively involved in the regulation of development and the maintenance of physiological functions. The dysregulation of RBFOX2 is closely associated with tumors, cardiovascular diseases, developmental defects and metabolic diseases. In this review, we summarize the regulatory functions of RBFOX2 in terms of both alternative and non-alternative splicing, the upstream regulatory factors of RBFOX2, and its relationship with disease etiology and progression, with the aim of providing a comprehensive understanding of the role of RBFOX2 and offering new insights for the study of RBFOX2.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"144 ","pages":"Article 105007"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145421505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction notice to “MICA/B expression in macrophage foam cells infiltrating atherosclerotic plaques” [Experimental and Molecular Pathology 97 (2014) 171–175]","authors":"Shunji Ikeshita,&nbsp;Yukiko Miyatake,&nbsp;Noriyuki Otsuka,&nbsp;Masanori Kasahara","doi":"10.1016/j.yexmp.2025.104981","DOIUrl":"10.1016/j.yexmp.2025.104981","url":null,"abstract":"","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"144 ","pages":"Article 104981"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of concern: \"1,25-Dihydroxyvitamin D3 enhances neural stem cell proliferation and oligodendrocyte differentiation\" [Experimental and Molecular Pathology 98 (2015) 240-245].","authors":"","doi":"10.1016/j.yexmp.2025.104985","DOIUrl":"https://doi.org/10.1016/j.yexmp.2025.104985","url":null,"abstract":"","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"144 ","pages":"104985"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145741652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SUMOylation and NEDDylation in kidney diseases","authors":"Zi-Han Chen ,&nbsp;Dan Li ,&nbsp;Jian-Yu Zhang ,&nbsp;Bo-Yu Wei ,&nbsp;Hai-Ling Zhao ,&nbsp;Ping Li ,&nbsp;Dan-Qian Chen","doi":"10.1016/j.yexmp.2025.105010","DOIUrl":"10.1016/j.yexmp.2025.105010","url":null,"abstract":"<div><div>Kidney disease poses a serious threat to human health and life, while the lack of specific therapeutic targets hinders the treatment of kidney disease. Emerging evidence shows that post-translational modifications (PTMs), particularly SUMOylation and NEDDylation, two ubiquitin-like modifications, are potential therapeutic targets for kidney disease. SUMOylation and NEDDylation participate in the treatment of kidney diseases by regulating different substrate proteins and signaling pathways. In renal ischemia-reperfusion injury, the promotion of LKB1 SUMOylation and the inhibition of NEDDylation modification facilitate renal fibrosis, and the increase of HIF-1α deSUMOylation contributes to attenuating apoptosis and oxidative stress in the kidneys. In diabetic kidney disease (DKD), the suppression of IKKγ SUMOylation attenuates NF-κB inflammatory signaling, while the inhibition of STAT1 SUMOylation and RBMX SUMOylation alleviates renal fibrosis. Additionally, inhibiting Notch1 signaling SUMOylation reduces podocyte apoptosis and glomerular endothelial cell injury, while the suppression of RhoA NEDDylation decreases inflammation and fibrosis in DKD. Accumulated studies display the therapeutic effect of the activators and inhibitors of SUMOylation and NEDDylation against kidney diseases, such as TAK-981 and MLN4924. Therefore, SUMOylation and NEDDylation function as promising therapeutic targets for kidney diseases, and their activators and inhibitors may serve as novel candidates.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"144 ","pages":"Article 105010"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145575959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}