Experimental and molecular pathology最新文献

{"title":"Genetic and epigenetic determinants of fetal alcohol spectrum disorders: Toward a precision medicine approach","authors":"Francesco Sessa ,&nbsp;Marco Carotenuto ,&nbsp;Davide Ferorelli ,&nbsp;Massimiliano Esposito ,&nbsp;Cristoforo Pomara ,&nbsp;Monica Salerno","doi":"10.1016/j.yexmp.2025.105002","DOIUrl":"10.1016/j.yexmp.2025.105002","url":null,"abstract":"<div><div>Fetal Alcohol Spectrum Disorders (FASD) encompass a continuum of neurodevelopmental and physical impairments resulting from prenatal alcohol exposure (PAE). Despite widespread recognition of ethanol's teratogenic effects, the clinical variability observed in FASD suggests a multifactorial etiology involving genetic, biochemical, epigenetic, and environmental influences. This review provides an integrative analysis of how genetic polymorphisms in key alcohol-metabolizing enzymes (ADH1B, ADH1C, ALDH2, CYP2E1, and CAT) modulate maternal and fetal susceptibility to ethanol and its toxic metabolite, acetaldehyde. These polymorphisms influence enzymatic activity, oxidative stress responses, and detoxification efficiency, thereby shaping fetal exposure and risk.</div><div>The review further explores maternal–fetal genotype interactions, gene–environment dynamics, and the timing of exposure as critical modulators of FASD outcomes. Epigenetic mechanisms, including DNA methylation, histone modifications, and microRNA regulation, are examined as mediators of long-term gene expression changes and neurodevelopmental disruption. Novel insights are provided into the roles of the 5-HTTLPR and orexin systems in neuropsychiatric vulnerability.</div><div>By synthesizing molecular, genetic, and clinical perspectives, this review advocates for a precision medicine approach to FASD prevention and management. It discusses the potential of genetic screening, predictive modeling, and theranoMiRNAs for risk stratification and early intervention. Importantly, it also addresses the translational challenges, including cost, feasibility, and the risk of false positives/negatives, that must be overcome to move from theory to clinical practice. These insights support the development of personalized, ethically grounded strategies to reduce fetal harm and improve outcomes in genetically and environmentally susceptible populations.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"144 ","pages":"Article 105002"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145267321","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":"Cell-specific functions of STAT3 in osteoarthritis and its therapeutic potential","authors":"Cai Zhang ,&nbsp;Jingyuan Gao ,&nbsp;Lu Chen ,&nbsp;Lei Xing ,&nbsp;Limin Li ,&nbsp;Xiaoli Hou ,&nbsp;Faming Tian","doi":"10.1016/j.yexmp.2025.104998","DOIUrl":"10.1016/j.yexmp.2025.104998","url":null,"abstract":"<div><div>Osteoarthritis (OA) represents a prevalent chronic joint disorder, which is pathologically characterized by cartilage degeneration. At present, effective therapeutic interventions for OA remains relatively infrequent, highlighting the urgent need for a deeper exploration of the underlying mechanisms of the disease and the development of novel, more effective treatments. A growing body of research has increasingly highlighted the pivotal role of signal transducer and activator of transcription 3 (STAT3), a critical downstream effector protein activated by a diverse array of cytokines, in mediating various physiological and pathological processes. STAT3 has been implicated in the pathophysiological progression of OA, influencing key aspects of disease development. This review concentrated on the notable role and molecular mechanisms of STAT3 signalling in the degeneration of cartilage and dysfunction of the subchondral bone, while synthesizing the most recent evidence regarding the therapeutic potential of targeting the STAT3 pathway for OA management. By concentrating on the inhibition of STAT3 signalling pathway, this review aimed to contribute to the translation of these findings into innovative, clinically relevant treatment strategies for OA.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"144 ","pages":"Article 104998"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155169","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 “Interferon alpha-2b inhibits negative-strand RNA and protein expression from full-length HCV1a infectious clone” [Experimental and Molecular Pathology 76 (2004) 242–252].","authors":"Ramesh Prabhu ,&nbsp;Virendra Joshi ,&nbsp;Robert F. Garry ,&nbsp;Frank Bastian ,&nbsp;Salima Haque ,&nbsp;Fredric Regenstein ,&nbsp;Swan Thung ,&nbsp;Srikanta Dash","doi":"10.1016/j.yexmp.2025.104999","DOIUrl":"10.1016/j.yexmp.2025.104999","url":null,"abstract":"","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"144 ","pages":"Article 104999"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228307","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":"Corrigendum to “Characteristics of liver fibrosis associated with chronic Opisthorchis felineus infection in Syrian hamsters and humans” [Experimental and Molecular Pathology 110 (2019) 104274]","authors":"Anna V. Kovner ,&nbsp;Maria Y. Pakharukova ,&nbsp;Galina A. Maksimova ,&nbsp;Viatcheslav A. Mordvinov","doi":"10.1016/j.yexmp.2025.104975","DOIUrl":"10.1016/j.yexmp.2025.104975","url":null,"abstract":"","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"144 ","pages":"Article 104975"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265790","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":"The association between abnormal glucose metabolism and rheumatoid arthritis","authors":"Xiaoyu Zhang,&nbsp;Fanyan Meng,&nbsp;Zhidan Wang,&nbsp;Shuang Ren,&nbsp;Jie Zhang","doi":"10.1016/j.yexmp.2025.105001","DOIUrl":"10.1016/j.yexmp.2025.105001","url":null,"abstract":"<div><div>The research has found that the incidence of rheumatoid arthritis (RA) combined with Type 2 Diabetes Mellitus (T2DM) and insulin resistance (IR) is higher than that in the general population. This indicates that there is an association mechanism between RA and abnormal glucose metabolism. IR is one of the main causes of T2DM, and high blood glucose levels are one of the main symptoms of T2DM. Therefore, revealing the intrinsic mechanism between RA and the abnormal glucose metabolism in T2DM becomes the key to treating RA complicated with T2DM. This article summarizes the mechanism of RA combined with T2DM, which is mainly caused by the disorder of glucose metabolism and the persistent presence of inflammatory mediators. The synovial hyperplasia, angiogenesis and bone destruction of RA interact with the abnormal glucose metabolism. Therefore, elaborating the intrinsic connection and interaction mechanism between abnormal glucose metabolism and RA, and summarizing the abnormal glucose metabolism phenomenon of increased prevalence of T2DM in RA patients in clinical practice, can provide a reference for future in-depth research on treatment plans related to abnormal glucose metabolism in RA.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"144 ","pages":"Article 105001"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145267322","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":"Prevalence and clinical significance of CBP deficiency and disturbed CBP expression in human cancer","authors":"Victoria Chirico ,&nbsp;Tabea Lenkeit ,&nbsp;Seyma Büyücek ,&nbsp;Katharina Möller ,&nbsp;Florian Lutz ,&nbsp;Florian Viehweger ,&nbsp;Martina Kluth ,&nbsp;Claudia Hube-Magg ,&nbsp;Christian Bernreuther ,&nbsp;Guido Sauter ,&nbsp;Andreas H. Marx ,&nbsp;Ronald Simon ,&nbsp;Till Krech ,&nbsp;Stefan Steurer ,&nbsp;Christoph Fraune ,&nbsp;Sarah Minner ,&nbsp;Natalia Gorbokon ,&nbsp;Maximilian Lennartz ,&nbsp;Eike Burandt ,&nbsp;Anne Menz ,&nbsp;Nina Schraps","doi":"10.1016/j.yexmp.2025.105012","DOIUrl":"10.1016/j.yexmp.2025.105012","url":null,"abstract":"<div><div>CBP (CREB-binding protein) is a ubiquitously expressed major histone modifier involved in the regulation of thousands of genes. In cancer, loss-of-function and overexpression can occur. To clarify the role of CBP expression, a tissue microarray containing 14,966 samples from 134 different tumor entities and 608 samples of 76 different normal tissues was analyzed by immunohistochemistry. In normal tissues, strong nuclear CBP staining was ubiquitously seen except of few cell types. Among 12,255 evaluable tumors, CBP staining was completely absent (CBP deficiency) in 226 (1.84 %) while 232 (1.89 %) showed only faint to moderate staining of a minority of cancer cells (substantial reduction, SR), 384 (3.13 %) weak, 3079 (25.12 %) moderate, and 8334 (68.00 %) strong CBP positivity. CBP deficiency or SR was common in endometrioid endometrial carcinoma (22.8 %), hepatocellular carcinoma (19.0 %), urothelial carcinoma (up to 17.4 %), serous endometrial carcinoma (12.5 %), and chromophobe renal cell carcinoma (RCC; 10.7 %). Less than 10 % CBP deficient or SR cases were seen in &gt;50 additional tumor categories. Among tumors with CBP expression, reduced expression was linked to high pT (<em>p</em> &lt; 0.0001), high UICC stage (<em>p</em> = 0.0005) and poor grade (<em>p</em> &lt; 0.0001) in clear cell RCC, high UICC stage (<em>p</em> = 0.0409) and distant metastasis (<em>p</em> = 0.0022) in papillary RCC, advanced pT stage (<em>p</em> = 0.0003) in colorectal carcinoma and invasive disease (p &lt; 0.0001) and L1 status (<em>p</em> = 0.0154) in urothelial carcinoma. High CBP expression was related to nodal metastasis in pancreatic adenocarcinoma (<em>p</em> = 0.0201). In conclusion, CBP deficiency is a rare event in many different tumor types. Reduced or absent CBP expression is linked to aggressive cancer phenotypes.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"144 ","pages":"Article 105012"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145620295","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":"Histopathological analysis reveals mild to moderate changes in BALB/c mice after short-term administration of a microemulsion loaded with epoxy-α-lapachone","authors":"Luiz Filipe Gonçalves-Oliveira ,&nbsp;Juliana Figueiredo Peixoto ,&nbsp;Bernardo Acácio Santini Pereira ,&nbsp;Nathalia Silva Carlos Oliveira ,&nbsp;Flávia de Oliveira Cardoso ,&nbsp;Davyson de Lima Moreira ,&nbsp;Franklin Silva-Souza ,&nbsp;Carlos Roberto Alves","doi":"10.1016/j.yexmp.2025.105006","DOIUrl":"10.1016/j.yexmp.2025.105006","url":null,"abstract":"<div><div>The development of innovative treatments for American Cutaneous Leishmaniasis is crucial due to severe side effects of current treatment and the emergence of non-responder parasites. To address such a challenge the incorporation of epoxy-α-lapachone (ELAP) into a microemulsion (ME), named ELAP-ME, represents a promising therapeutic approach. In previous studies, ELAP-ME demonstrated efficacy in controlling infection in the BALB/c-<em>Leishmania</em> (<em>Leishmania</em>) <em>amazonensis</em> model, advancing in the technology readiness level with a drug prototype. To further validate its potential as a drug prototype, the histopathological effects of ELAP-ME were investigated in healthy BALB/c mice as a preclinical approach stage. Mice were administered with a fixed dose of ELAP-ME microemulsion (∼7 μg/kg) and evaluated at different short-term after administration (4, 12, and 24 h). Histopathological analysis of the liver, kidney, lung, heart, and brain revealed only mild alterations. These findings confirm the low toxicity profile of ELAP-ME, highlighting its safety and supporting its continued advancement as a pharmacological alternative for the treatment of leishmaniasis.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"144 ","pages":"Article 105006"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145421453","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":"Therapeutic strategies in cystinosis: A focus on cysteamine and beyond","authors":"Angelo Santoro ,&nbsp;Yuri Vincenzo Ferrara ,&nbsp;Alfonso De Angelis","doi":"10.1016/j.yexmp.2025.104995","DOIUrl":"10.1016/j.yexmp.2025.104995","url":null,"abstract":"<div><div>Cystinosis is a autosomal recessive lysosomal storage disorder caused by mutations in the CTNS gene, which encodes cystinosin, a cystine transporter. The defective function of cystinosin leads to cystine accumulation in the lysosome, resulting in progressive multi-organ damage. Cystinosis manifests early in life, with nephropathic cystinosis typically presenting in infancy with renal Fanconi syndrome, leading to chronic kidney disease and end-stage renal disease if untreated. Diagnosis relies on clinical evaluation, corneal examination, leukocyte cystine quantification, and CTNS genetic testing. In the present review, both cysteamine-based and non-cysteamine therapeutic approaches for the treatment of cystinosis are discussed. Cysteamine therapy, reduces intracellular cystine levels and delays disease progression, significantly improving patient outcomes. However, cysteamine requires lifelong adherence and has limitations, including gastrointestinal side effects and frequent dosing. Kidney transplantation remains a therapeutic option for end-stage renal disease, although extra-renal complications persist. Novel therapeutic strategies are under investigation to address these limitations, including improved cysteamine formulations, prodrugs, and small molecules. Additional approaches include gene therapy, stem cell-based interventions, mRNA-based treatments, and the targeted degradation of cystine crystals. Continued research and multidisciplinary management are essential to enhancing the prognosis and quality of life for individuals affected by cystinosis.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"144 ","pages":"Article 104995"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144989487","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":"Corrigendum to “Upregulation of CDK7 in gastric cancer cell promotes tumor cell proliferation and predicts poor prognosis” [Experimental and Molecular Pathology 100 (2016) 514–521]","authors":"Qiuhong Wang ,&nbsp;Manhua Li ,&nbsp;Xunlei Zhang ,&nbsp;Hua Huang ,&nbsp;Jianfei Huang ,&nbsp;Jing Ke ,&nbsp;Haifang Ding ,&nbsp;Jinzhang Xiao ,&nbsp;Xiaohang Shan ,&nbsp;Qingqing Liu ,&nbsp;Bojun Bao ,&nbsp;Lei Yang","doi":"10.1016/j.yexmp.2025.104974","DOIUrl":"10.1016/j.yexmp.2025.104974","url":null,"abstract":"","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"144 ","pages":"Article 104974"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224873","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":"Glycocalyx shedding as a clinical biomarker in critical illness","authors":"Ayako Inoda ,&nbsp;Keiko Suzuki ,&nbsp;Hiroyuki Tomita ,&nbsp;Hideshi Okada","doi":"10.1016/j.yexmp.2025.104997","DOIUrl":"10.1016/j.yexmp.2025.104997","url":null,"abstract":"<div><div>The endothelial glycocalyx, a carbohydrate-rich layer lining the vascular endothelium, plays a critical role in maintaining vascular homeostasis by regulating permeability, leukocyte adhesion, and inflammatory signaling. Its degradation has been implicated in endothelial dysfunction and organ damage in various diseases. Biomarkers derived from glycocalyx components, particularly Syndecan-1 (SDC-1) and heparan sulfate (HS), can be detected in blood and urine, providing a potential window into vascular injury. In this narrative review, we explore the clinical potential of glycocalyx-derived biomarkers, with a focus on SDC-1, in a broad spectrum of conditions, including sepsis, coronavirus disease, acute respiratory distress syndrome, kidney diseases, cardiovascular disorders, autoimmune diseases, cancer, trauma, and pregnancy-related complications. We highlight the pathophysiological mechanisms of glycocalyx degradation, assess the diagnostic and prognostic utility of SDC-1, and summarize emerging therapeutic strategies to preserve glycocalyx integrity. Given their strong association with disease severity and outcomes, glycocalyx-derived biomarkers may enable earlier diagnosis, improved risk stratification, and personalized treatment, supporting more informed clinical decision-making across diverse medical conditions.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"144 ","pages":"Article 104997"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145227163","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}