Experimental and molecular pathology最新文献

{"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, Virendra Joshi, Robert F Garry, Frank Bastian, Salima Haque, Fredric Regenstein, Swan Thung, 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":" ","pages":"104999"},"PeriodicalIF":3.7,"publicationDate":"2025-10-03","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":"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":"2025-10-03","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}

{"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":"2025-09-25","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":"Automated quantification of collagen proportionate area correlates with molecular and histological markers of fibrosis in CCl4-treated rats","authors":"Bernie Efole ,&nbsp;Mathilde Mouchiroud ,&nbsp;Alexandra Dubé ,&nbsp;Andréa Allaire ,&nbsp;Sébastien M. Labbé ,&nbsp;Cindy Serdjebi ,&nbsp;Olivier Barbier ,&nbsp;Alexandre Caron","doi":"10.1016/j.yexmp.2025.104996","DOIUrl":"10.1016/j.yexmp.2025.104996","url":null,"abstract":"<div><div>Liver fibrosis results from chronic liver injury and is characterized by excessive accumulation of extracellular matrix due to sustained wound-healing responses. Although histological evaluation remains the gold standard for fibrosis assessment, its subjectivity can limit reproducibility. In this study, we evaluated an automated image analysis software, MorphoQuant, for liver fibrosis quantification in a rat model of CCl4-induced liver injury. Male Wistar rats were treated with CCl4 or vehicle for six weeks, and fibrosis severity was assessed using both the conventional Ishak staging system and automated quantification of collagen proportionate area (CPA). Automated CPA strongly correlated with Ishak stage, liver index, and plasma aminotransferase levels. Additionally, CPA values were significantly associated with the expression of fibrosis-related genes and macrophage infiltration, highlighting the software's ability to assess both fibrosis progression and inflammatory responses. These findings support the use of MorphoQuant as a robust, reader-independent tool that enhance analytical consistency in preclinical models of liver fibrosis.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"144 ","pages":"Article 104996"},"PeriodicalIF":3.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145060865","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":"2025-09-04","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":"Drug-eluting coronary stents mediate inflammation-associated protein signature in an experimental in vitro study.","authors":"Vera Paar, Xuanchao Feng, Kristen Kopp, Fitore Marmullaku, Uta C Hoppe, Lukas J Motloch, Michael Lichtenauer","doi":"10.1016/j.yexmp.2025.104991","DOIUrl":"10.1016/j.yexmp.2025.104991","url":null,"abstract":"<p><p>Drug eluting stents (DES) are a first-line treatment for ischemic heart diseases. Due to their direct contact with the blood stream, late stent thromboses are a common complication. Thrombosis and inflammation are tightly linked to each other, and are characterized by the activation of inflammatory cells and the secretion of cytokines and chemokines. To date, the influence of DES on the activation of the inflammatory cascade and its corresponding players has not yet been investigated. We performed an in vitro study to observe any potential response of isolated human peripheral blood mononuclear cells (PBMCs) to the structure and drug-coating of different DES. PBMCs from healthy volunteers were incubated with different DES types for 48 h. We measured the secretion of cytokines and chemokines, as well as cell adhesion molecules, and selected growth factors by ELISA. DES were found to significantly increase the cytokine and chemokine secretion of IL-1β, IL-6, IL-8, and ICAM-1, as well as the growth factors ANG and FGF-basic. We further showed that zotarolimus presents with the lowest inflammation-associated protein expression. Our data further revealed that the inflammatory reaction is highly dependent on the DES size, material, and the polymer type of the DES coating. Finally, we tendentially showed that thinner alloys are associated with a lower inflammatory reaction. Our results indicate that DES may potentially lead to an increased inflammatory reaction, considering the different DES designs and properties. This would potentially help to further improve composition and drug selection.</p>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"143 ","pages":"104991"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144816114","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":"Platelet-derived growth factor-C contributes to kidney inflammation in experimental hypertension with little effect on the peritubular capillary network","authors":"Ina V. Martin ,&nbsp;Christian Dippel ,&nbsp;Eva M. Buhl ,&nbsp;Robert Göllinger ,&nbsp;Katja Ermert ,&nbsp;Jürgen Floege ,&nbsp;Eleni Stamellou ,&nbsp;Ute Raffetseder ,&nbsp;Rafael Kramann ,&nbsp;Tammo Ostendorf","doi":"10.1016/j.yexmp.2025.104994","DOIUrl":"10.1016/j.yexmp.2025.104994","url":null,"abstract":"<div><h3>Background and aims</h3><div>Platelet-Derived Growth Factor (PDGF)-C plays a significant role in kidney fibrosis, angiogenesis, and hypertension. While its involvement in the healing of damaged glomerular capillaries is well recognized, its function in kidney peritubular capillaries (PTCs) remains less understood. Therefore, this study investigates the role of PDGF-C in PTCs under both homeostatic conditions and experimentally angiotensin II (AngII)-induced hypertension.</div></div><div><h3>Materials and methods</h3><div>We utilized mice with systemic PDGF-C antagonism or conditional deletion of endothelial-derived PDGF-C (<em>Cdh5-cre::Pdgfc</em>^{<em>flox/flox</em>}) in an AngII-induced hypertension model. The PTC network, glycocalyx, and inflammatory parameters in the kidneys were analyzed and quantified using qPCR, electron microscopy, and fluorescence microscopy.</div></div><div><h3>Results</h3><div>Systemic antagonism of PDGF-C in the AngII model reduced peritubular accumulation of PDGF receptor-expressing mesenchymal cells and the expression of <em>Ccl2</em>, <em>Plat</em> and <em>Nos3</em>, while PTC density and glycocalyx-regulating genes remained unaffected. Conditional deletion of endothelial cell-derived PDGF-C did not affect peritubular accumulation of mesenchymal cells, blood pressure or genes associated with angiogenesis; it also had no impact on the PTC network or glycocalyx. Notably, a reduction in inflammatory infiltrates was observed in the hypertensive <em>Cdh5-cre::Pdgfc</em>^{<em>flox/flox</em>} -mice.</div></div><div><h3>Conclusion</h3><div>Despite influencing certain parameters critical for endothelial homeostasis, such as PDGFR⁺ pericyte recruitment following systemic PDGF-C antagonism during hypertension, PDGF-C has minimal effects on the PTC network. Conversely, both systemic and endothelial cell-derived PDGF-C modulate the inflammatory response associated with hypertension in the kidney. Our findings help mitigate safety concerns about pharmacological PDGF-C targeting and its impact on peritubular capillaries.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"143 ","pages":"Article 104994"},"PeriodicalIF":3.7,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144907621","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":"Peroxidasin expression is increased in intratumoural capillaries and in proximal tubular cells adjacent to clear cell renal cell carcinoma.","authors":"Roberto Silva ,&nbsp;Jorge Reis Almeida ,&nbsp;Ana Rita Coelho ,&nbsp;Isabel Brandão ,&nbsp;Bárbara Gomes ,&nbsp;Inês Soares Alencastre ,&nbsp;João Paulo Oliveira","doi":"10.1016/j.yexmp.2025.104993","DOIUrl":"10.1016/j.yexmp.2025.104993","url":null,"abstract":"<div><div>Peroxidasin (PXDN), is a heme peroxidase with a critical role in the crosslinking of type IV collagen, being essential for basement membrane integrity. Overexpression of PXDN has been associated with poor clinical outcomes in many cancers; however, little is currently known about its role in renal cell carcinoma (RCC). In this study, we characterized the expression of PXDN in tumour tissue and adjacent non-neoplastic tissue from cases of clear cell renal cell carcinoma (ccRCC), chromophobe RCC (chRCC), and renal oncocytoma using immunohistochemistry. Our results revealed increased PXDN expression in the intratumoural capillaries of ccRCC compared to other tumour types, including oncocytoma. Additionally, there was a notable increase in PXDN expression in the proximal tubular epithelial cells of non-neoplastic adjacent parenchyma in ccRCC cases compared to the same region in oncocytomas. These findings suggest, for the first time, that PXDN may play a role in tumour angiogenesis, potentially promoting metastases and malignancy. Furthermore, PXDN may be involved in the crosstalk between the tumour and adjacent tissues, a mechanism warranting further investigation.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"143 ","pages":"Article 104993"},"PeriodicalIF":3.7,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144866366","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":"Research progress of sarcopenia: Diagnostic advancements, molecular mechanisms, and therapeutic strategies","authors":"Hao-lin Wang ,&nbsp;Long-long Liu ,&nbsp;Ze-yu Tan ,&nbsp;Yuan Zhou ,&nbsp;Jing Zhang ,&nbsp;Lin Zhai ,&nbsp;Qian Xie ,&nbsp;Rong-hua Liu","doi":"10.1016/j.yexmp.2025.104992","DOIUrl":"10.1016/j.yexmp.2025.104992","url":null,"abstract":"<div><div>Muscle atrophy or loss is an important sign of human aging. As the aging society approaches and human lifespan prolongs, sarcopenia has emerged as one of the significant risks influencing the quality of life of the elderly. Sarcopenia is a progressive geriatric syndrome characterized by the deterioration of skeletal muscle mass and function, which can result in an increased risk of falls, fractures, restricted physical activity, disability, mortality, and a remarkable escalation in the risk of cardiovascular diseases among the elderly. This work synthesizes recent advances in sarcopenia research, critically evaluating diagnostic frameworks, histopathological hallmarks, and molecular pathways driving disease progression. Additionally, we provide an in-depth analysis of evidence-based exercise and nutritional interventions, identifying key research gaps. These insights offer valuable references for future research on sarcopenia and clinical management, as well as lifestyle interventions such as exercise and nutrition.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"143 ","pages":"Article 104992"},"PeriodicalIF":3.7,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144829736","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 interplay involving oxidative stress and autophagy: Mechanisms, implications, and therapeutic opportunities","authors":"Noha A. Gouda ,&nbsp;Assem Zhakupova ,&nbsp;Ahmed M. Abdelaal ,&nbsp;Firdos Ahmad ,&nbsp;Ahmed Elkamhawy","doi":"10.1016/j.yexmp.2025.104989","DOIUrl":"10.1016/j.yexmp.2025.104989","url":null,"abstract":"<div><div>Reactive oxygen species (ROS) are extremely reactive molecules produced during cellular metabolism, which play important roles in signaling and immune responses. Excessive ROS accumulation results in oxidative stress and cellular damage. As a result, autophagy (a cellular recycling process) is induced to overcome oxidative stress conditions by eliminating impaired cellular components. By selectively targeting and degrading dysfunctional mitochondria and peroxisomes through mitophagy and pexophagy, respectively, cells can effectively reduce ROS accumulation. Conversely, oxidative stress can disrupt autophagy, impairing protein aggregate clearance and thereby exacerbating ROS accumulation. In this review, we discuss the complex correlation between oxidative stress and autophagy, highlighting the mechanisms of regulation and their pathological implications. Additionally, we discuss the latest advances and challenges in developing autophagy-modulating therapies.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"143 ","pages":"Article 104989"},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144757616","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}