Experimental and molecular pathology最新文献_第2页

Optimized manual multiplex immunofluorescence protocol for human nasal tissue 优化人鼻组织人工多重免疫荧光检测方案

IF 3.7 4区医学

Experimental and molecular pathology Pub Date : 2026-03-01 Epub Date: 2026-01-29 DOI: 10.1016/j.yexmp.2026.105028

S. Klingenstein , J. Grünig , P.H. Neckel , B. Hirt , S. Liebau , M. Klingenstein

{"title":"Optimized manual multiplex immunofluorescence protocol for human nasal tissue","authors":"S. Klingenstein , J. Grünig , P.H. Neckel , B. Hirt , S. Liebau , M. Klingenstein","doi":"10.1016/j.yexmp.2026.105028","DOIUrl":"10.1016/j.yexmp.2026.105028","url":null,"abstract":"<div><h3>Summary</h3><div>The human nose is a complex sensory organ responsible for air filtration, moisture regulation, heat exchange, and odor detection. To resolve its cellular and structural heterogeneity—including regions traditionally associated with respiratory and olfactory functions—we applied multiround multiplex immunofluorescence to human postmortem nasal samples. We optimized a manual workflow combining autofluorescence quenching and efficient antibody stripping for frontal nasal and olfactory bulb sections. Multiple published protocols were systematically tested and adapted, with particular emphasis on preserving tissue integrity at bone–soft tissue interfaces. Using this approach, we performed multiplex staining on full nasal sections with five antibodies across three rounds, followed by a validation round with GFAP. Marker panels included K5 (basal cells), TUBB3 (neuronal elements), ANXA1 and E-cadherin (epithelial borders), COLIV (basement membrane), and GFAP (glial/ensheathing cells).</div><div>This optimized method enables spatial mapping of distinct cell types within intact human nasal tissue and provides a robust platform for future studies on epithelial organization and structural remodeling in health and disease.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"145 ","pages":"Article 105028"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074125","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}

引用次数: 0

Preliminary evidence that adipose tissue contributes to serum proprotein convertase subtilisin/kexin type 9 levels in murine models of metabolic liver injury 初步证据表明，脂肪组织有助于小鼠代谢性肝损伤模型中血清蛋白转化酶枯草杆菌素/ keexin 9型水平的提高

IF 3.7 4区医学

Experimental and molecular pathology Pub Date : 2026-03-01 Epub Date: 2026-01-28 DOI: 10.1016/j.yexmp.2026.105029

Sabrina Krautbauer , Florian Weber , Gerhard Liebisch , Christa Buechler

{"title":"Preliminary evidence that adipose tissue contributes to serum proprotein convertase subtilisin/kexin type 9 levels in murine models of metabolic liver injury","authors":"Sabrina Krautbauer , Florian Weber , Gerhard Liebisch , Christa Buechler","doi":"10.1016/j.yexmp.2026.105029","DOIUrl":"10.1016/j.yexmp.2026.105029","url":null,"abstract":"<div><div>Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with obesity. Excess cholesterol, the hepatic and circulating levels of which are regulated by proprotein convertase subtilisin/kexin type 9 (PCSK9), exacerbates MASLD. Data on hepatic and circulating PCSK9 protein expression in MASLD are inconsistent, and PCSK9 levels in different adipose tissues have not been well studied. Here, we used two MASLD mouse models that develop hepatic steatosis, one with weight gain and one with weight loss. These models enable distinguishing between the effects of obesity and MASLD. In the high-fat diet model, hepatic PCSK9 protein was normal. PCSK9 protein was increased in the serum and epididymal fat of the mice. In mice fed a methionine-choline-deficient diet, PCSK9 protein was normal in the liver, brown fat, subcutaneous fat, epididymal, and perirenal adipose tissue. Serum PCSK9 levels were reduced, suggesting that the lower fat mass of these mice contributed to the reduction. It is noteworthy that PCSK9 expression was low in adipocytes compared to hepatocytes. In addition, stromal vascular cells residing within adipose tissue contribute to PCSK9 protein levels in adipose tissue. PCSK9 protein was similar in subcutaneous, epididymal, and perirenal adipose tissue and was lowest in brown adipose tissue, indicating a more prominent expression in white adipose tissues. The current study shows that PCSK9 is expressed in both white and brown adipose tissues, and suggests that obesity rather than liver steatosis is associated with higher serum PCSK9 levels.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"145 ","pages":"Article 105029"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074126","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}

引用次数: 0

Expression of concern: "LncRNAs and miRNAs participate in determination of sensitivity of cancer cells to cisplatin" [Experimental and Molecular Pathology 123 (2021) 104602]. 关注表达：“LncRNAs和miRNAs参与确定癌细胞对顺铂的敏感性”[Experimental and Molecular Pathology 123(2021) 104602]。

IF 3.7 4区医学

Experimental and molecular pathology Pub Date : 2026-03-01 Epub Date: 2025-12-22 DOI: 10.1016/j.yexmp.2025.105020

引用次数: 0

Corrigendum to “NVP-BEZ235 enhances autophagy and ameliorates cognitive deficits by targeting tauopathies” [Experimental and Molecular Pathology 143 (2025) 104988] “NVP-BEZ235通过靶向tau病变增强自噬和改善认知缺陷”[实验和分子病理学143(2025)104988]的勘误表。

IF 3.7 4区医学

Experimental and molecular pathology Pub Date : 2026-03-01 Epub Date: 2026-01-11 DOI: 10.1016/j.yexmp.2025.105018

Ifat Alsharif

引用次数: 0

Stereological quantification of tumor infiltrating immune cells as predictor of immunotherapy in metastatic melanoma 肿瘤浸润免疫细胞的体视定量作为转移性黑色素瘤免疫治疗的预测因子

IF 3.7 4区医学

Experimental and molecular pathology Pub Date : 2026-03-01 Epub Date: 2025-12-11 DOI: 10.1016/j.yexmp.2025.105016

Lenka Vaňková , Jiří Polívka , Věra Křížková , Samuel Vokurka , Ondřej Fiala , Monika Holubová , Kristýna Pivovarčíková , Inka Třešková , Tereza Knížková , Jan Říčař , Radek Kučera , Martin Pešta

{"title":"Stereological quantification of tumor infiltrating immune cells as predictor of immunotherapy in metastatic melanoma","authors":"Lenka Vaňková , Jiří Polívka , Věra Křížková , Samuel Vokurka , Ondřej Fiala , Monika Holubová , Kristýna Pivovarčíková , Inka Třešková , Tereza Knížková , Jan Říčař , Radek Kučera , Martin Pešta","doi":"10.1016/j.yexmp.2025.105016","DOIUrl":"10.1016/j.yexmp.2025.105016","url":null,"abstract":"<div><div>Immunotherapy by immune checkpoint inhibitors (ICIs) revolutionized the treatment of melanoma patients. Tumor-infiltrating immune cells (TIICs) play a crucial role in antitumor immunity activated by ICIs. However, ICIs treatment may be associated with serious immune-related adverse events (irAEs). The aim of the study was to identify the key immune cells and molecules of the tumor microenvironment responsible for the treatment effects and risk of irAEs through immunohistochemical quantification of TIICs. We analyzed metastases (FFPE) of 28 melanoma patients treated with ICIs. Multilevel sampling and stereological quantification were used to assess TIICs identified immunohistochemically by the markers CD1a, CD1d, CD3, CD4, CD8, CD20, CD56, CD68, FOXP3, including immune checkpoint molecules LAG3, PD1, PD-L1. In lymph node metastases, higher infiltration of PD-L1, CD8-positive cells and lower infiltration of CD1a-positive cells predicted response to ICIs (<em>P</em> ≤ 0.05, P ≤ 0.05, P ≤ 0.05, resp.). In all metastasis's subtypes, higher expression of PD-L1 was predictor of response to immunotherapy (P ≤ 0.05). Lower PD-L1 expression (P ≤ 0.05) and lower CD3 expression (<em>P</em> ≤ 0.001) were associated with irAEs. Higher infiltration of CD8-positive T lymphocytes was associated with longer progression-free survival (<em>P</em> = 0.0166) as well as overall survival (<em>P</em> = 0.0454). Stereological quantification of specific immune cells in melanoma metastases, such as T-lymphocytes (CD3), cytotoxic T-lymphocytes (CD8), dendritic cells (CD1a) and PD-L1-positive cells, may predict ICIs treatment efficacy or the risk of irAEs. High infiltration of metastatic tissue by CD8-positive T cells is important for long-term favorable therapeutic response to ICIs.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"145 ","pages":"Article 105016"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145735408","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}

引用次数: 0

25-nitro-20-epi-vitamin D analogue with anti-proliferative and cytoprotective properties: Biological and pharmacological evaluation 具有抗增殖和细胞保护特性的25-硝基-20-外延维生素D类似物：生物学和药理学评价。

IF 3.7 4区医学

Experimental and molecular pathology Pub Date : 2026-03-01 Epub Date: 2026-02-23 DOI: 10.1016/j.yexmp.2026.105036

Uxía Gómez-Bouzó , Carole Peluso-Iltis , Sandra Barreiro , Carlos Fernandes , Lieve Verlinden , Annemieke Verstuyf , Fernanda Borges , Natacha Rochel , Generosa Gómez , Yagamare Fall

{"title":"25-nitro-20-epi-vitamin D analogue with anti-proliferative and cytoprotective properties: Biological and pharmacological evaluation","authors":"Uxía Gómez-Bouzó , Carole Peluso-Iltis , Sandra Barreiro , Carlos Fernandes , Lieve Verlinden , Annemieke Verstuyf , Fernanda Borges , Natacha Rochel , Generosa Gómez , Yagamare Fall","doi":"10.1016/j.yexmp.2026.105036","DOIUrl":"10.1016/j.yexmp.2026.105036","url":null,"abstract":"<div><div>We report the synthesis and pharmacological evaluation of <strong>UG-635</strong>, a novel 25-nitro vitamin D analogue bearing a 20-epimeric configuration. Cytotoxicity studies in SH-SY5Y neuroblastoma and HepG2 hepatocarcinoma cells showed that <strong>UG-635</strong> is well tolerated at low concentrations but reduces viability at higher doses. Importantly, <strong>UG-635</strong> demonstrated protective effects against oxidative stress in neuronal cells and exhibited anti-proliferative activity in breast cancer (MCF7) and osteoblast (MC3T3-E1) models, with efficacy comparable to calcitriol. Structural and crystallographic analyses revealed efficient binding to the vitamin D receptor (VDR), stabilizing its active conformation through favorable interactions with anchoring histidines. These findings highlight <strong>UG-635</strong> as a promising vitamin D analogue with potential pharmacological relevance in cancer and neurodegenerative disease contexts, combining anti-proliferative and cytoprotective properties.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"145 ","pages":"Article 105036"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147283197","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}

引用次数: 0

Cannabinoids and skin cancer: Mechanistic insights, therapeutic potential, and translational perspectives 大麻素和皮肤癌：机制的见解，治疗潜力，和翻译的观点

IF 3.7 4区医学

Experimental and molecular pathology Pub Date : 2026-03-01 Epub Date: 2026-01-31 DOI: 10.1016/j.yexmp.2026.105027

Ashutosh Pareek , Rashi Gupta , Aaushi Pareek , Jenny Wilkerson , Lance R. McMahon , Gautam Sethi , Anil Chuturgoon

{"title":"Cannabinoids and skin cancer: Mechanistic insights, therapeutic potential, and translational perspectives","authors":"Ashutosh Pareek , Rashi Gupta , Aaushi Pareek , Jenny Wilkerson , Lance R. McMahon , Gautam Sethi , Anil Chuturgoon","doi":"10.1016/j.yexmp.2026.105027","DOIUrl":"10.1016/j.yexmp.2026.105027","url":null,"abstract":"<div><div>Skin cancer represents a significant global healthcare challenge, with rising incidence and persistent gaps in effective long-term management. Recent evidence has identified the endocannabinoid system as an emerging therapeutic target offering novel pharmacological approaches for the prevention and treatment of various skin cancers. Cannabinoids, through modulation of the endocannabinoid system, have demonstrated antitumor activity by inhibiting tumor proliferation, angiogenesis, invasion, and metastasis and by inducing apoptosis and autophagy in malignant cells. This review synthesizes the most recent preclinical evidence on phytocannabinoids, endocannabinoids, and synthetic cannabinoids in melanoma and non-melanoma skin cancers, delineating receptor-dependent and receptor-independent mechanisms. Additionally, emerging cannabinoid-based delivery strategies, particularly cannabidiol formulations designed to enhance skin penetration and therapeutic efficacy, are critically examined. Despite encouraging preclinical findings, clinical translation remains limited by scarce skin-cancer-specific trials, variability in cannabinoid preparations, and uncertainties around dosing and safety. Consequently, robust mechanistic studies and well-designed clinical trials are required to validate cannabinoids' therapeutic potential and guide their integration into future skin cancer treatment paradigms.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"145 ","pages":"Article 105027"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074127","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}

引用次数: 0

Seizure susceptibility relates to microglial TREM2 expression and morphology in a multiple repeated low-dose kainic acid model 在多次重复低剂量kainic酸模型中，癫痫易感性与小胶质细胞TREM2的表达和形态有关

IF 3.7 4区医学

Experimental and molecular pathology Pub Date : 2026-03-01 Epub Date: 2025-12-06 DOI: 10.1016/j.yexmp.2025.105014

Hyo Jung Shin , In Soo Kim , Minwoo Kim , Seung Yeon Jung , Dong Woon Kim , Joon Won Kang

{"title":"Seizure susceptibility relates to microglial TREM2 expression and morphology in a multiple repeated low-dose kainic acid model","authors":"Hyo Jung Shin , In Soo Kim , Minwoo Kim , Seung Yeon Jung , Dong Woon Kim , Joon Won Kang","doi":"10.1016/j.yexmp.2025.105014","DOIUrl":"10.1016/j.yexmp.2025.105014","url":null,"abstract":"<div><div>Microglia, the resident immune cells of the brain, play a critical role in maintaining homeostasis. In this study, we investigated changes in microglial phenotype associated with seizure susceptibility. Kainic acid (KA) was injected intraperitoneally, and when seizures reached Racine stage 4/5, administration was stopped, and mice were monitored for 60 min. Only mice that showed behavioral convulsive status epilepsy (SE) in the first experiment received a second KA injection 2 weeks later. Using this model, we observed changes in brain tissue and microglial phenotype according to seizure susceptibility. We also analyzed gene expression patterns associated with microglial phagocytosis in a publicly available hippocampal transcriptome microarray dataset (GSE88992) from mice injected with KA. After the initial low-dose KA repeat injection, the number of injections required to induce SE during the secondary injection was compared with the initial injection, and mice were categorized into seizure-resistant (SR, <em>n</em> = 26, no SE), seizure-tolerant (ST, <em>n</em> = 11, SE after ≥2 injections), and seizure-susceptible (SS, <em>n</em> = 15, SE after ≤2 injections) groups. Neuronal loss was observed in all seizure groups, but the extent varied across hippocampal regions. Microglial phenotypes in the hippocampus showed significant differences between groups. Immunofluorescence staining further confirmed that triggering receptor expressed on myeloid cells (TREM2) expression was increased in microglia in the SS group. Using a model that classifies seizure resistance, tolerance, and susceptibility, we observed significant differences in microglial phenotypes and TREM2 expressions between groups. This study highlights the role of microglia in the progression from first seizures to subsequent seizures, a critical step in the development of epilepsy.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"145 ","pages":"Article 105014"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145683828","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}

引用次数: 0

Corrigendum to “Wharton's jelly-derived nanovesicles for targeting intervertebral disc degeneration” [Experimental and Molecular Pathology 144 (2025) 105011] “Wharton’s jelly-derived nanovesic泡靶向椎间盘退变”的勘误表[Experimental and Molecular Pathology 144(2025) 105011]。

IF 3.7 4区医学

Experimental and molecular pathology Pub Date : 2026-03-01 Epub Date: 2026-02-16 DOI: 10.1016/j.yexmp.2026.105034

Letizia Penolazzi , Alice Zaramella , Anna Chierici , Paola Bisaccia , Maria Pina Notarangelo , Anna Maria Tolomeo , Elisabetta Lambertini , Anna Alessia Saponaro , Tommaso Colangelo , Michela Pozzobon , Roberta Piva

引用次数: 0

Mechanisms and strategies for reversing NK cell exhaustion in tumor immunotherapy 肿瘤免疫治疗中逆转NK细胞衰竭的机制和策略。

IF 3.7 4区医学

Experimental and molecular pathology Pub Date : 2026-03-01 Epub Date: 2026-02-05 DOI: 10.1016/j.yexmp.2026.105031

Lingtong Zhi , Yuqing Wang , Zixing Zhao , Yabin Guo , Kaiwen Wang , Wenhui He , Changjiang Guo , Zhiyuan Niu , Wuling Zhu , Xuan Zhang

{"title":"Mechanisms and strategies for reversing NK cell exhaustion in tumor immunotherapy","authors":"Lingtong Zhi , Yuqing Wang , Zixing Zhao , Yabin Guo , Kaiwen Wang , Wenhui He , Changjiang Guo , Zhiyuan Niu , Wuling Zhu , Xuan Zhang","doi":"10.1016/j.yexmp.2026.105031","DOIUrl":"10.1016/j.yexmp.2026.105031","url":null,"abstract":"<div><div>Natural Killer (NK) cells play a crucial role in the body's innate immune system, distinguished by their ability to target a wide array of tumors through diverse killing strategies. Following the intense focus on T cells, NK cells have emerged as a key player in immunotherapy. Recent advancements in NK cell-based cancer treatments, including adoptive cell therapy, immune checkpoint inhibition, recombinant cytokine therapies, and nanomedicines, have demonstrated promising outcomes both in vitro and in vivo. As research into NK cell-based therapies intensifies, evidence is mounting that NK cells undergo phenotypic changes, acquiring characteristics of exhaustion. Key features comprise reduced proliferative capacity, diminished cytokine production, altered receptor expression, as well as compromised lymph node homing and Tumor Microenvironment (TME) persistence. NK cell exhaustion not only reduces NK cell efficacy and number in solid tumor therapies, but it also plays a crucial role in treatment resistance and tumor cell evasion. Understanding the mechanisms behind NK cell exhaustion and developing strategies to counteract it within the suppressive TME are of paramount importance. In this review, we delineate the maturation and development of NK cells, emphasize the phenotypic characteristics and underlying mechanisms of NK cell exhaustion, systematically review the methods to mitigate NK cell exhaustion, and thoroughly discuss the current limitations of NK cell immunotherapy. Ultimately, we aim to provide potential solutions and future directions for enhancing NK cell-based cancer treatments.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"145 ","pages":"Article 105031"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131572","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}

引用次数: 0