Khadija Boukholda, Bakhta Aouey, Yassine Chtourou, Eman Elbayoumi, Melania Guerrero-Hue, Cristina García-Caballero, Fatma Boukholda, Mercedes Vallejo-Mudarra, Bilqees Sameem, Fatiha Chigr, Michèle Bouchard, Juan Antonio Moreno, Hamadi Fetoui
{"title":"Silica nanoparticles trigger striatal oxidative stress, apoptosis, and histopathological alterations: in vivo and in silico molecular docking insights.","authors":"Khadija Boukholda, Bakhta Aouey, Yassine Chtourou, Eman Elbayoumi, Melania Guerrero-Hue, Cristina García-Caballero, Fatma Boukholda, Mercedes Vallejo-Mudarra, Bilqees Sameem, Fatiha Chigr, Michèle Bouchard, Juan Antonio Moreno, Hamadi Fetoui","doi":"10.1007/s00418-025-02424-y","DOIUrl":"https://doi.org/10.1007/s00418-025-02424-y","url":null,"abstract":"<p><p>Humans are increasingly exposed to silica nanoparticles (SiNPs) from environmental and occupational sources, raising significant concerns about their safety. Despite growing applications, data on their neurotoxic effects, particularly those involving oxidative/nitrosative imbalance and striatal damage, remain limited. This study aimed to elucidate the mechanisms of SiNP-induced neurotoxicity in the striatum, a brain region crucial for motor control and learning, using a rat model. Subacute intraperitoneal administration of SiNPs (25 and 100 mg/kg bw/day for 28 days) resulted in a marked increase in lipid peroxidation (LPO), reactive oxygen species (ROS), nitrite (NO), and protein carbonyl content, alongside a significant reduction in the activity of antioxidant enzymes, viz. superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as glutathione (GSH). Additionally, cholinergic [acetylcholinesterase (AChE) and b1utyrylcholinesterase (BChE)] and membrane-bound adenosine triphosphate (ATP)ase (Na<sup>+</sup>/K<sup>+</sup>, Mg<sup>2+</sup>, and Ca<sup>2+</sup> ATPase) activities were significantly reduced in the striatum. Immunofluorescence and immunohistochemistry revealed elevated expression of antioxidant markers, particularly nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Quantitative reverse-transcriptase real-time polymerase chain reaction (qRT-PCR) analysis demonstrated upregulation of pro-apoptotic genes (Bax, p53, caspase-9/3) and downregulation of the anti-apoptotic gene Bcl-2, leading to an increased Bax/Bcl-2 ratio. Complementary in silico molecular docking studies showed that SiNPs exhibit notable binding affinities toward Nrf2, HO-1, AChE, and BChE. Collectively, these findings indicate that SiNPs induce striatal neurotoxicity via oxidative/nitrosative stress-mediated apoptosis, involving activation of Nrf2/HO-1, cholinergic disruption, and apoptotic signaling pathways.</p>","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"163 1","pages":"97"},"PeriodicalIF":2.1,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Uğur Akcan, Haşim Bakbak, Ecem Ayvaz, Müge Atış, Canan Uğur Yılmaz, Nurcan Orhan, Tuğba Kotil, Nadir Arıcan, Bülent Ahıshalı, Mehmet Kaya
{"title":"Methyl-beta-cyclodextrin and myriocin alleviate blood-brain barrier impairment in septic rats.","authors":"Uğur Akcan, Haşim Bakbak, Ecem Ayvaz, Müge Atış, Canan Uğur Yılmaz, Nurcan Orhan, Tuğba Kotil, Nadir Arıcan, Bülent Ahıshalı, Mehmet Kaya","doi":"10.1007/s00418-025-02421-1","DOIUrl":"https://doi.org/10.1007/s00418-025-02421-1","url":null,"abstract":"<p><p>In this study, the effect of targeting plasma membranes by depleting cholesterol and inhibiting sphingolipid synthesis using methyl-beta-cyclodextrin (MβCD) and myriocin, respectively, on blood-brain barrier (BBB) integrity was investigated in rats under septic conditions induced by cecal ligation and puncture (CLP). Horseradish peroxidase (HRP) and Evans blue (EB) tracers were used to assess BBB permeability. Caveolin (Cav)-1, claudin-3 and -5, and glucose transporter (Glut)-1 expression was assessed using immunofluorescence staining. In septic rats, MβCD or myriocin significantly attenuated the increased BBB permeability to both tracers. Upon MβCD administration, Cav-1 immunoreactivity decreased in the cerebral cortex; however, it increased markedly in the hippocampus in CLP-operated animals. MβCD and myriocin treatments to septic rats increased claudin-3 immunoreactivity in brain regions, and the difference reached statistical significance with the former treatment. In septic rats, claudin-5 immunoreactivity in brain regions was significantly decreased by MβCD and increased by myriocin. In CLP-operated animals, MβCD and myriocin treatments increased Glut-1 immunoreactivity in the brain regions, with the differences reaching statistical significance in the cerebral cortex and hippocampus by the former, while in only the cerebral cortex by the latter treatment. In conclusion, our results suggest that altering lipid profiles of plasma membranes by MβCD and myriocin can alleviate BBB disruption in septic conditions and, hence, may account for a novel therapeutic modality.</p>","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"163 1","pages":"95"},"PeriodicalIF":2.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Henry Bautista-Amorocho, Jorge Alexander Silva-Sayago
{"title":"Mechanical-enzymatic isolation and characterization of primary human gingival epithelial cells for reproducible in vitro oral mucosa models.","authors":"Henry Bautista-Amorocho, Jorge Alexander Silva-Sayago","doi":"10.1007/s00418-025-02422-0","DOIUrl":"10.1007/s00418-025-02422-0","url":null,"abstract":"<p><p>The establishment of reliable in vitro oral mucosa models is essential for advancing studies in epithelial barrier function, wound healing, and host-microbe interactions. However, the widespread use of immortalized cell lines such as HaCaT or TR146 limits physiological relevance owing to altered differentiation profiles and genetic drift. In this study, we developed a robust mechanical-enzymatic protocol for isolating and expanding primary human gingival keratinocytes from healthy gingival explants without feeder layers. The resulting cells demonstrated high viability, maintained consistent proliferative capacity across passages, and exhibited characteristic cobblestone morphology. Comprehensive phenotypic validation included immunofluorescence and immunohistochemistry confirming strong expression of epithelial markers CK18, AE1/AE3, and MUC1, with absence of the mesenchymal marker vimentin. Transcriptomic analysis using RT-qPCR corroborated epithelial lineage fidelity, revealing stable MUC1 expression and lack of MUC5AC transcripts, indicative of a nonglandular phenotype. Metabolic competence was supported by WST-1 assays that correlated strongly with manual cell counts, underscoring functional viability. Importantly, AGS and 293T/17 cell lines were processed in parallel as orthogonal controls to confirm assay specificity and lineage discrimination. Under rigorously standardized, within-laboratory conditions, our workflow yielded high interdonor concordance in epithelial identity and growth kinetics across a young-adult cohort (n = 3), supporting its use as a practical primary-cell platform for downstream applications. Generalizable reproducibility-across age strata, operators, and sites-will require formal, preregistered multicenter validation. By mitigating limitations inherent to immortalized lines, this approach enables more accurate investigations of epithelial biology and strengthens the reliability of in vitro experimental systems relevant to oral regenerative medicine and mucosal immunology.</p>","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"163 1","pages":"96"},"PeriodicalIF":2.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12507993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The role of progenitor cells and telocytes in the ameliorative effect of Coenzyme Q10 on isoproterenol-induced cardiotoxicity in rats.","authors":"Sinem İnal, Yonca Betil Kabak","doi":"10.1007/s00418-025-02426-w","DOIUrl":"https://doi.org/10.1007/s00418-025-02426-w","url":null,"abstract":"<p><p>Coenzyme Q10 (CoQ10) is an antioxidant known for its potential protective effects against various types of cardiac injury. The aim of this study was to determine the protective effects of CoQ10 on cardiomyocytes, telocytes and progenitor cells in rats with isoproterenol (ISO)-induced cardiotoxicity. A total of 60 Sprague-Dawley rats were divided into six groups (n = 10): Group I: control, Group II: saline control, Group III: oil control, Group IV: ISO, Group V: CoQ10, Group VI: ISO and CoQ10. Isoproterenol was administered intraperitoneally at a dose of 85 mg/kg twice on the eighth and ninth days, and CoQ10 was administered by oral gavage at a daily dose of 20 mg/kg. Heart tissue samples were collected and analysed at the end of the study. CoQ10 reduced ISO-induced cardiac degeneration, necrosis, inflammatory infiltration and fibrosis. The stimulation of cell cycle activators such as histone H3 and proliferating cell nuclear antigen (PCNA) was found to play a role in the repair of cardiac injury in the cardiomyocytes known to be postmitotic. An increase in c-Kit and CD34 stem cells was seen with the beneficial effect of CoQ10 (P < 0.05). The presence of telocytes, which play an important role in cardiac regeneration, was visualised by double CD34-c-Kit and CD34-vimentin immunofluorescence staining. The results indicate that CoQ10, through its antioxidant effect, ameliorates cardiac lesions caused by ISO, induces a limited number of cell cycle activators in cardiomyocytes and interstitial cells and has a positive effect on the increase of progenitor cells in the heart.</p>","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"163 1","pages":"94"},"PeriodicalIF":2.1,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michal Španko, Lucie Pfeiferová, Eliška Drobná Krejčí, Michal Kolář, Pavel Dundr, Jaroslav Valach, Karel Smetana, Lukáš Lacina
{"title":"Gamma smooth muscle actin as a new potential marker of cancer-associated fibroblasts.","authors":"Michal Španko, Lucie Pfeiferová, Eliška Drobná Krejčí, Michal Kolář, Pavel Dundr, Jaroslav Valach, Karel Smetana, Lukáš Lacina","doi":"10.1007/s00418-025-02419-9","DOIUrl":"10.1007/s00418-025-02419-9","url":null,"abstract":"<p><p>Cancer-associated fibroblasts (CAFs) represent an important component of the cancer ecosystem, influencing the broad scale of biological properties of tumour cells, including the capacity for metastasis formation. An important CAF subpopulation, known as myCAFs, typically expresses α-smooth muscle actin. Transcriptomic analysis demonstrated that activated fibroblasts isolated from various pathological tissues also express the ACTG2 gene encoding γ-smooth muscle actin. This was further validated by immunocytochemistry. Using the scratch test in vitro, it was possible to demonstrate that γ-smooth muscle actin may be associated with the epithelial-mesenchymal transition, which was also shown by transcriptomic analysis. The presence of γ-smooth muscle actin-positive fibroblasts in histopathological sections of human tumours verified the expression of this protein as a new potential marker of CAFs.</p>","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"163 1","pages":"93"},"PeriodicalIF":2.1,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Increased Fos immunoreactivity in astrocytes in the raphe pallidus under hypoxia, not hypercapnia.","authors":"Kouki Kato, Risa Serizawa, Takuya Yokoyama, Nobuaki Nakamuta, Yoshio Yamamoto","doi":"10.1007/s00418-025-02420-2","DOIUrl":"10.1007/s00418-025-02420-2","url":null,"abstract":"<p><p>The raphe pallidus (RPa), a part of the caudal medullary raphe nucleus, has been suggested to participate in respiratory regulation. Therefore, hypoxia and hypercapnia are expected to affect the expression of Fos, a marker of cellular activation, in the RPa; however, there is currently no consensus on Fos expression in the RPa under hypoxic and hypercapnic conditions. The present study investigated the distribution of Fos expression in the RPa of rats exposed to hypoxia (10% O<sub>2</sub>), hypercapnia (8% CO<sub>2</sub>), and hypercapnic hypoxia (10% O<sub>2</sub> and 8% CO<sub>2</sub>) for 2 h. To confirm whether activation of the RPa affects respiratory function, an electrical stimulation was applied to the RPa of anesthetized rats. The stimulation induced a significant increase in the respiratory rate, which was similar to the respiratory changes induced by hypoxia. An immunohistochemical analysis revealed two types of cells in the RPa: serotonin-immunoreactive neurons and SOX9-immunoreactive astrocytes. Hypoxia significantly increased Fos immunoreactivity in astrocytes in the rostral region of the RPa, but did not affect Fos immunoreactivity in serotonergic neurons. In contrast, hypercapnia and hypercapnic hypoxia did not affect Fos immunoreactivity in either cell type in any region. These results suggest that astrocytes in the RPa are specifically activated by hypoxia and actively contribute to the respiratory response to hypoxia.</p>","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"163 1","pages":"91"},"PeriodicalIF":2.1,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12443861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unveiling the intricacies of exosome biology: from biogenesis to therapeutic applications.","authors":"Angel Mendonca, Aparajita Acharjee, Yash Sansare, Sujatha Sundaresan","doi":"10.1007/s00418-025-02418-w","DOIUrl":"10.1007/s00418-025-02418-w","url":null,"abstract":"<p><p>Exosomes are small membrane-bound nanovesicles that are secreted by cells when multivesicular bodies merge with the plasma membrane. These particles have been demonstrated to carry specific proteins, lipids and genetic components that are exclusive to each cell type. These compounds can be selectively taken up by cells in close proximity or at a distance, even after being released, thus altering their biological response. Therefore, the regulated manufacturing of exosomes, the exact makeup of their contents and their capacity to selectively interact with particular cells are highly important in the field of biology because of the immense potential of exosomes as noninvasive diagnostic biomarkers and therapeutic nanocarriers. This review presents a comprehensive examination and evaluation of the most recent progress in comprehending the regulatory mechanisms of exosome formation, the molecular composition of exosomes and the approaches utilised in exosome research. Furthermore, this review focuses on the potential use of exosomes as promising markers for the diagnosis and prognosis of medical conditions, owing to their specific associations with cellular lineage and state. In addition, the potential role of exosomes as vehicles for the delivery of medicines and genes for therapeutic applications is unraveled. The study of exosomes is currently in a nascent phase. Acquiring a thorough understanding of the subcellular constituents and processes implicated in exosome generation, together with their specific cell targeting, can yield valuable insights into their physiological roles.</p>","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"163 1","pages":"92"},"PeriodicalIF":2.1,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"July in focus in HCB.","authors":"Douglas J Taatjes, Jürgen Roth","doi":"10.1007/s00418-025-02409-x","DOIUrl":"https://doi.org/10.1007/s00418-025-02409-x","url":null,"abstract":"","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"163 1","pages":"90"},"PeriodicalIF":2.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bao Zhang, Shuaiyu Wang, Yaning Wang, Chen Liang, Hongbo Zhang
{"title":"MyoAnalyst: an ImageJ plugin for accurate and automatic myofiber segmentation and analysis in skeletal muscle cross sections.","authors":"Bao Zhang, Shuaiyu Wang, Yaning Wang, Chen Liang, Hongbo Zhang","doi":"10.1007/s00418-025-02414-0","DOIUrl":"https://doi.org/10.1007/s00418-025-02414-0","url":null,"abstract":"<p><p>Quantifying myofiber size is essential for assessing the health and function of skeletal muscle. Although several ImageJ plugins are currently available for myofiber segmentation and size quantification, significant challenges remain-most notably limited accuracy and poor compatibility with hematoxylin and eosin (H&E)-stained skeletal muscle cross sections. In this study, we introduce MyoAnalyst, an ImageJ plugin designed to enable automated analysis of both immunofluorescence (IF)- and H&E-stained skeletal muscle cross sections. Compared to existing ImageJ plugins, MyoAnalyst delivers enhanced segmentation sensitivity and superior boundary delineation accuracy across both healthy and injured muscle tissue stained with IF. Importantly, it also supports fully automated analysis of H&E-stained sections. With its intuitive graphical interface and batch processing capabilities, MyoAnalyst provides a potentially efficient tool for myofiber size quantification in both research and clinical settings.</p>","PeriodicalId":13107,"journal":{"name":"Histochemistry and Cell Biology","volume":"163 1","pages":"89"},"PeriodicalIF":2.1,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}