Acta histochemica最新文献

{"title":"Silencing Livin gene expression by RNA interference enhanced the chemotherapeutic sensitivity of drug-resistant osteosarcoma cells to doxorubicin","authors":"Lei Huang ,&nbsp;Xiaobin Zeng ,&nbsp;Kaimin Xiao ,&nbsp;Sen Tang ,&nbsp;Kuo Sun","doi":"10.1016/j.acthis.2025.152249","DOIUrl":"10.1016/j.acthis.2025.152249","url":null,"abstract":"<div><h3>Background</h3><div>Osteosarcoma is one of the most common malignant tumors in children and adolescents. It occurs in the metaphysis of long bones and is a type of aggressive malignant tumor. Although there are treatment methods such as surgery and chemotherapy, the mortality and disability of osteosarcoma patients are still high. With the emergence of more and more chemotherapy resistance, it is necessary to find new therapies to improve the chemotherapy sensitivity of osteosarcoma.</div></div><div><h3>Methods</h3><div>Drug-resistant MG-63 and U2OS cell strain was established in vitro by continuous exposure of human osteosarcoma cells to doxorubicin at gradually increasing concentrations，then determined for resistance index to doxorubicin by MTT method，for transcriptions of Livin mRNA by real-time polymerase chain reaction（RT⁃PCR），and for expressions of Livin proteins by Western blot．The technology of gene recombination was used to construct the eukaryotic expression vector pSilencer3.1-H1 neo-Livin. Then the pSilencer3.1-H1 neo-Livin was transfected into drug-resistant MG-63 cell by using Lipofectmine 2000. Expressions of Livin mRNA and protein in the transfected cells were respectively measured by RT-PCR and Western blot. The distribution of cell cycle phase and apoptosis were determined by flow cytometry. The analysis of chemotherapeutic sensitivity of drug-resistant MG-63 cell to doxorubicin was performed by MTT.</div></div><div><h3>Results</h3><div>The recombinant eukaryotic expression vector pSilencer3.1-H1 neo-Livin was successfully constructed. The result of inverted microscope revealed that the drug-resistant MG-63 cell were irregularity and morphological diversity. Compared with those in osteosarcoma cells，the transcription levels of Livin mRNA and protein in drug-resistant osteosarcoma cell increased（P＜0.05）．The flow cytometry analysis showed there was higher percentage of apoptosis in transfected drug-resistant MG-63 cell. Compared with control groups，the expression of Livin mRNA and protein were both significantly decreased in the transfected drug-resistant osteosarcomacell（P＜0.05）. We also observed that suppression of Livin expression in osteosarcoma cells increased their chemosensitivity to doxorubicin.</div></div><div><h3>Conclusion</h3><div>This study showed that Livin shRNA inhibited the proliferation level and increased the sensitivity of drug-resistant osteosarcoma cell to doxorubicin, suggested that Livin is involved in drug resistance of human osteosarcoma and may serve as a promising therapeutic target for osteosarcoma.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 2","pages":"Article 152249"},"PeriodicalIF":2.3,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683336","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":"The significance of Itga8 and Vangl2 in kidney development: Insights from yotari mice","authors":"Nikola Pavlović ,&nbsp;Nela Kelam ,&nbsp;Anita Racetin ,&nbsp;Andrea Gelemanović ,&nbsp;Natalija Filipović ,&nbsp;Patricija Bajt ,&nbsp;Yu Katsuyama ,&nbsp;Katarina Vukojević","doi":"10.1016/j.acthis.2025.152247","DOIUrl":"10.1016/j.acthis.2025.152247","url":null,"abstract":"<div><div>The permanent kidney develops from the metanephros through the interaction of the ureteric bud (UB) and metanephric mesenchyme (MM). Congenital anomalies of the kidney and urinary tract (CAKUT) are common prenatal diagnoses, and genetic factors play a critical role in their development. This study explores the involvement of Integrin alpha-8 (Itga8) and Van Gogh-like 2 (Vangl2) proteins in kidney development, using the <em>yotari</em> (<em>yot</em>) mouse model, which harbors a mutation in the <em>Dab1</em> gene, disrupting Reelin signaling. Immunofluorescence was employed to analyze the spatiotemporal expression patterns of these proteins in embryonic and postnatal kidney samples. Our results show that Itga8 and Vangl2 expression is significantly higher in the embryonic kidneys of <em>yot</em> mice than those of wt mice. However, the two groups observed no significant differences in the temporal expression of these proteins in postnatal kidneys. Spatially, Itga8 was most strongly expressed in the metanephric mesenchyme and renal vesicles/immature glomeruli. At the same time, Vangl2 showed the highest expression in the metanephric mesenchyme, renal vesicles/immature glomeruli, and collecting ducts in <em>yot</em> mice. Our findings suggest that the <em>Dab1</em> mutation disrupts the expression of Itga8 and Vangl2, contributing to kidney developmental defects associated with CAKUT phenotypesThis increased expression suggests a disruption in the normal regulation of these proteins, likely due to the Dab1 mutation, which impairs Reelin signaling. Still, the exact mechanism through which the Reelin/Dab1 pathway influences the expression of examined markers remains to be elucidated. These results offer valuable insights into the factors associated with kidney malformations and suggest potential therapeutic targets for CAKUT abnormalities.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 2","pages":"Article 152247"},"PeriodicalIF":2.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642841","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":"Exploring the potential of stem cell therapy: Applications, types, and future directions","authors":"KeerthiShri Boopathy ,&nbsp;Thirunavukkarasu Palaniyandi ,&nbsp;Maddaly Ravi ,&nbsp;Mugip Rahaman Abdul Wahab ,&nbsp;Gomathy Baskar ,&nbsp;Safia Obaidur Rab ,&nbsp;Mohd Saeed ,&nbsp;Vishal M. Balaramnavar","doi":"10.1016/j.acthis.2025.152237","DOIUrl":"10.1016/j.acthis.2025.152237","url":null,"abstract":"<div><div>One of the most significant treatment approaches now accessible is stem cell therapy. Over the last few decades, a lot of study has been done in this field, and this fascinating feature of plasticity could have therapeutic uses. The potential of stem cells to restore function lost as a result of disease, trauma, congenital defects, and age has made stem cell research a key priority for scientific and medical organizations across the world. Stem cells are a crucial topic of study in regenerative medicine because of their capacity to replace, repair, or regenerate damaged cells, tissues, or organs. As a result, stem cell therapy is being used as a treatment strategy for a number of illnesses. Because stem cells may proliferate indefinitely and generate vast quantities of differentiated cells needed for transplantation, they hold enormous promise for regenerative medicine. Stem cells can be reprogrammed from adult cell types or originate from embryonic or fetal origins. Depending on their availability and place of origin, stem cells can be totipotent, pluripotent, multipotent, oligopotent, or unipotent. With stem cell treatment, many ailments, including diabetes, liver disease, infertility, wounds and traumas, neurological disorders, cardiovascular disease, and cancer, might be cured. Various types of stem cell treatment are described in this review along with their applications in different therapeutic fields, ethical considerations, and advantages and disadvantages.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 2","pages":"Article 152237"},"PeriodicalIF":2.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509520","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":"EFNA1 promotes the tumorigenesis and metastasis of cervical cancer by phosphorylation pathway and epithelial-mesenchymal transition","authors":"Xiaorui Dong ,&nbsp;Xixi Chen ,&nbsp;Mengling Xue ,&nbsp;Yina Zhang ,&nbsp;Peiyue Jiang","doi":"10.1016/j.acthis.2025.152236","DOIUrl":"10.1016/j.acthis.2025.152236","url":null,"abstract":"<div><h3>Background</h3><div>Cervical cancer (CC) is a common gynecological disease that seriously threatens women’s health. This study aims to explore key genes and pathways related to CC prognosis through bioinformatics, providing new insights for further treatment of CC.</div></div><div><h3>Methods</h3><div>CC patient data were analyzed from the public databases. The enrichment analyses explored the roles and pathways of CC-related differentially expressed genes (DEGs). A prognostic key gene was identified using Venn diagrams and subjected to survival analysis. Gene Set Enrichment Analysis (GSEA) was employed to investigate the potential pathways of key genes. Correlations between the key gene and clinical features were examined. The function of the key gene was validated through immunohistochemistry, flow cytometry, transwell, MTT, and Western blot assays <em>in vitro</em> and <em>in vivo</em>.</div></div><div><h3>Results</h3><div>Our research identified 2459 upregulated genes among DEGs between healthy and tumor cervical tissues. These DEGs were primarily enriched in the PI3K-AKT and MAPK pathways. Moreover, EFNA1 was recognized as a key prognostic gene in CC, with elevated expression compared to normal tissue. A negative correlation between EFNA1 levels and patient survival rates was corroborated by Kaplan-Meier analysis. Furthermore, EFNA1 expression correlated with the cancer stage and was linked to antigen presentation, folate synthesis, and IL-17 signaling. Knockdown of EFNA1 enhanced apoptosis and reduced migration, invasion, and proliferation <em>in vitro</em> and <em>in vivo</em>, inhibiting EMT and MAPK pathways.</div></div><div><h3>Conclusion</h3><div>This study revealed the key signaling pathways in CC progression and identified EFNA1 as a crucial prognostic biomarker, potentially impacting CC treatment.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 2","pages":"Article 152236"},"PeriodicalIF":2.3,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143474528","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":"Mechanoresponsive patterns of KLF2, 4, 5, and 6 expression differ among subclones from a single mammary tumor","authors":"Rafaela Marocci Lima Pimenta ,&nbsp;Cara Skon-Hegg ,&nbsp;Teresa Rose-Hellekant ,&nbsp;Jon Holy","doi":"10.1016/j.acthis.2025.152238","DOIUrl":"10.1016/j.acthis.2025.152238","url":null,"abstract":"<div><div>A number of Krüppel-like transcription factor (KLF) family members display mechanoresponsive behaviors, and function as mechanosensitive transcription factors. There are many normal and pathological conditions where their roles in mechanotransduction and mechanoadaptation are not well understood, however. In this study, two basic questions regarding KLF mechanoresponsiveness were addressed: 1) are KLF 2, 4, 5, and 6 expressed at different levels among subclones of tumor cells adapted to specific microenvironmental conditions; and 2) is the expression of these KLFs responsive to rapid changes in the physical environment? To address these questions, the heterogeneous and differentially metastatic murine mammary tumor subclones 4T1, 4T07, and 67NR were subjected to physical changes in their culture conditions, and KLF responses assessed. The results show that the expression of different KLFs exhibit distinct responses to reductions in cell tension, as well as cell detachment from 2D and 3D environments. KLF2 and 4 expression is rapidly and temporarily induced upon release of cells from a stiff 2D substrate into liquid suspension culture in all three subclones, and similar responses are observed in two of the subclones upon the release of tension in 3D collagen gel cultures. By contrast, expression patterns of KLF5 and 6 were generally less affected by physical changes in most, but not all, of the cell lines examined. These results support the concept that KLFs differentially participate in transducing physical differences among intratumoral neighborhoods into distinct responses among heterogeneous subclones, thereby contributing to tumor cell behavioral complexity.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 2","pages":"Article 152238"},"PeriodicalIF":2.3,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464519","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":"Aberration of CA3 functionally mediates the pathogenesis of Cardiomyocyte hypertrophy in a miR-138–5p dependent manner","authors":"Tingting Chu ,&nbsp;Qinghua Han ,&nbsp;Hongtao Shi ,&nbsp;Chao Li ,&nbsp;Qi Ma ,&nbsp;Peng Li ,&nbsp;Fang Wang ,&nbsp;Jing Zhang","doi":"10.1016/j.acthis.2025.152233","DOIUrl":"10.1016/j.acthis.2025.152233","url":null,"abstract":"<div><div>Cardiomyocyte hypertrophy (CDH) is a critical factor in heart disease, leading to heart failure and increased mortality. Despite extensive research, the precise molecular mechanisms underlying CDH remain unclear. In our study, we conducted total RNA sequencing on blood-derived exosomes from 11 CDH patients and 8 healthy donors. This analysis identified differentially expressed genes (DEGs), which we further validated using real-time qPCR and ROC analysis to demonstrate their diagnostic potential in clinical samples. To explore the functional role of CA3 in CDH, we manipulated its expression using the AAV9 vector in TAC (transverse aortic constriction) rat models(N = 6). We observed a significant increase in CA3 expression in both the blood of CDH patients and TAC rat models. Knockdown of Ca3 using the AAV9 vector resulted in improved cardiac function in TAC rats (N = 6), as evidenced by a ∼30 % reduction in LVEF% (left ventricular ejection fraction) and LVFS% (left ventricular fractional shortening) compared to Sham-operated controls. Additionally, LV (left ventricular) mass and the HW/BW (heart weight to body weight ratio) were significantly higher in the TAC groups. Mechanistically, we identified miR-138–5p as a direct regulator of CA3 through the StarBase bioinformatics tool. This interaction was experimentally validated using a dual-luciferase reporter assay and real-time qPCR. We found that miR-138–5p expression was down-regulated in both CDH patients and TAC rat models. Restoration of miR-138–5p expression mitigated the phenotypes induced by Ca3 overexpression. Our findings reveal a novel miR-138–5p/CA3 axis involved in the pathogenesis of CDH, suggesting potential therapeutic avenues for this heart disease.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 1","pages":"Article 152233"},"PeriodicalIF":2.3,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143349664","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":"Effect of chloroquine on autophagy and the severity of caerulein-induced acute pancreatitis in mice","authors":"Manish Kumar Sharma ,&nbsp;Kumari Priyam ,&nbsp;Punit Kumar ,&nbsp;Pramod Kumar Garg ,&nbsp;Tara Sankar Roy ,&nbsp;Tony George Jacob","doi":"10.1016/j.acthis.2025.152234","DOIUrl":"10.1016/j.acthis.2025.152234","url":null,"abstract":"<div><div>Impaired autophagy is implicated in the pathogenesis of caerulein-induced model of acute pancreatitis (AP). Chloroquine blocks the fusion of autophagosome and lysosome and affects completion of the cellular autophagic flux. Adult, male, Swiss albino mice (20–25 g) were divided into four groups- 1, 2, 3 and 4 of 6 mice each. Mice in Group1 were given 8, hourly intraperitoneal injections of normal saline. Group 2 was also given intraperitoneal injections of chloroquine (60 mg/Kg) at 14 h and 30-min prior to first injection of normal saline. Mice in Groups 3 and 4 given 8, hourly intraperitoneal injections of caerulein (50 µg /Kg/dose). Group 4 also received chloroquine as Group 2. After sacrifice at the 9th hour in CO₂-chamber, blood was drawn for amylase activity and cytokines estimation (IL-6, TNF-α, GM-CSF, IL-1β and IL-10) and pancreas was harvested for histopathology, transmission electron microscopy (TEM) and immunoblotting (LC3II, Beclin 1, SQSTM1, RIPK1, P65, Caspase-3, RIPK3, HMGB1). The relative expression of SQSTM1 and the autophagic vacuole area was higher in groups 2, 3 and 4 (p &lt; 0.05), suggestive of increased impairment of autophagic flux. Autolysosome count was significantly increased in group 3 in comparison to group 1 (p = 0.0049). Autolysosome area was also increased in group 4 in comparison to group 3 (p = 0.031), which suggested impairment of autophagy. Total histopathological score and amylase activity were equivalent in groups 3 and 4. RIPK1 in pancreas and TNF-α level in plasma were more in group 4 than 3 (p = 0.014, 0.02, respectively). Expression of Caspase-3, was lesser in group 4 than 3 (p &lt; 0.001). Expression of HMGB1was more in group 4 than 3 (p = 0.046). Chloroquine enhances necrosis and inflammation in caerulein-induced pancreatitis.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 1","pages":"Article 152234"},"PeriodicalIF":2.3,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143132646","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":"Spatiotemporal distribution of Wnt signaling pathway markers in human congenital anomalies of kidney and urinary tract","authors":"Ilija Perutina ,&nbsp;Nela Kelam ,&nbsp;Mirko Maglica ,&nbsp;Anita Racetin ,&nbsp;Azer Rizikalo ,&nbsp;Natalija Filipović ,&nbsp;Ivana Kuzmić Prusac ,&nbsp;Marko Bošnjak ,&nbsp;Josip Mišković ,&nbsp;Boris Kablar ,&nbsp;Nasrollah Ghahrani ,&nbsp;Katarina Vukojević","doi":"10.1016/j.acthis.2025.152235","DOIUrl":"10.1016/j.acthis.2025.152235","url":null,"abstract":"<div><div>This study aimed to investigate the spatiotemporal expression patterns of key markers involved in regulating the canonical and non-canonical Wnt pathway during human fetal kidney development, comparing healthy (CTRL) and congenital anomalies of the kidney and urinary tract (CAKUT) affected kidneys. Human fetal kidneys, ranging from the 18th to the 38th developmental weeks, including various CAKUT phenotypes (horseshoe, dysplastic, duplex and hypoplastic), underwent double immunofluorescence microscopy analysis following antibody staining. Immunoreactivity levels were quantified in different kidney structures, and expression dynamics were assessed using linear and nonlinear regression modeling techniques. The study revealed a decrease in the overall protein expression of acetylated α-tubulin during normal kidney development, while the highest percentage of positive cells was observed in the horseshoe kidney (HK), thus disturbing microtubule composition in normal cell division and differentiation. Additionally, a continuous decrease of inversin-positive cells in hypoplastic (HYP) and duplex kidneys (UD), but the exponential growth of DVL-1 expression score in dysplastic kidneys (DYS) with developmental age, result in suppression of final kidney differentiation by continuous canonical Wnt signaling activation, thus supporting the essential role of the switch from canonical to non-canonical Wnt pathway in nephrogenesis. Furthermore β-catenin-positive cells in dysplastic and hypoplastic kidney exhibited the highest percentage of positive signal, with a decline in β-catenin positive cells over time in the control group, indicating disturbances in transition from canonical to non-canonical Wnt pathway in CAKUT-affected kidneys. The findings suggest that the crosstalk between canonical and non-canonical Wnt signaling pathways is crucial for normal nephrogenesis, highlighting their potential roles in normal and dysfunctional kidney development.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 1","pages":"Article 152235"},"PeriodicalIF":2.3,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143132647","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":"3D examination reveals increased destruction of alpha-actin-positive structures in advanced follicular lymphoma stages","authors":"Katharina Geib ,&nbsp;Sonja Scharf ,&nbsp;Hendrik Schäfer ,&nbsp;Sylvia Hartmann ,&nbsp;Martin-Leo Hansmann ,&nbsp;Patrick Wurzel","doi":"10.1016/j.acthis.2025.152232","DOIUrl":"10.1016/j.acthis.2025.152232","url":null,"abstract":"<div><div>Follicular lymphoma (FL) represents the most prevalent subtype of non-Hodgkin’s-lymphoma in Western Europe and the United States. While the examination of two-dimensional histological slides remains the gold standard method for diagnosing FL stages, three-dimensional analysis provides additional insights, particularly regarding cellular morphology, spatial relationships and network connectivity. This investigation assessed the tumor-related morphological destruction of fibroreticular cell (FRC) networks bordering germinal centres in FL. A confocal laser scanning technology and a digital three-dimensional analysis system were used. Quantitive measurements included the length of fibroblastic reticular walls surrounding the germinal centres as well as the size of the gaps and holes within these structures. Three-dimensional analysis revealed progressive structural degradation and a reduction in mechanical barrier integrity, with differences observed between low- and high-grade FL. High-grade FL exhibited greater network destruction. Fibroblastic reticular cell networks’ wall length demonstrated a consistent decline across all grades. The lengths of these walls and wall-like structures in FL grades 1 or 2 were similar to reactive germinal centres seen in lymphadenitis, as well as the gap size. The gaps are thought to be responsible for B- and T-cell exchange. This work demonstrated the massive destruction of neoplastic germinal centres in grades 3a and 3b FL. In grade 3b, this was accompanied by a likely dysfunctional mechanical border of the germinal centre and the near-complete loss of structural integrity. Under physiological conditions, gaps and holes regulate lymphoid traffic. Under reactive conditions, only a few specific T-cells can access the germinal centre. Under neoplastic conditions, the diameter of these gaps increases as grades increase, culminating in complete structural disruption in grade 3b. The mechanical destruction was found to begin at one pole of the germinal centre, as evidenced by localized decay and fragmentation of FRC walls on one side. Fibroblastic reticular cell networks are critical for maintaining chemokine gradients to ensure compartmentalisation of lymphoid structures. Their ongoing degradation in FL of the networks leads to a morphological loss of function. This is due to the blurring of various lymph node zones.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 1","pages":"Article 152232"},"PeriodicalIF":2.3,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063085","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":"New insights into persistent corneal subepithelial infiltrates following epidemic keratoconjunctivitis: The first case report with ultrastructural and immunohistochemical investigations","authors":"Rita Mencucci ,&nbsp;Michela Cennamo ,&nbsp;Irene Rosa ,&nbsp;Daniele Guasti ,&nbsp;Matilde Buzzi ,&nbsp;Eleonora Sgambati ,&nbsp;Mirca Marini ,&nbsp;Mirko Manetti","doi":"10.1016/j.acthis.2025.152231","DOIUrl":"10.1016/j.acthis.2025.152231","url":null,"abstract":"<div><div>Epidemic keratoconjunctivitis (EKC) is one of the most severe clinical manifestations of human adenovirus ocular surface infection, which may lead to the formation of subepithelial infiltrates (SEIs) in the anterior corneal stroma in 20–50 % of cases. SEIs may be asymptomatic or give rise to corneal aberrations and visual impairment for months or years after acute infection, despite treatments. Here, we describe the ultrastructural and immunophenotypic features of the anterior corneal stroma of a patient who underwent superficial anterior lamellar keratoplasty (SALK) surgery to remove corneal opacities related to clinically significant and steroid-unresponsive, long-lasting SEIs after adenoviral EKC. Before femtosecond laser-assisted SALK surgical intervention, the patient underwent in vivo confocal microscopy that showed a cluster of hyperreflective inflammatory cells within the basal epithelium, associated to an abnormal sub-basal nerve plexus with a fragmented nervous component appearance. The areas corresponding to the SEIs appeared as roundish hyperreflective spots with undefined borders. Transmission electron microscopy analysis of the excised anterior corneal button revealed the presence of giant stromal cells displaying myofibroblast-like features immediately beneath the Bowman’s layer. Such abnormal cells exhibited ultrastructural signs of endoplasmic reticulum stress and autophagy, and were positive for markers of activated fibroblasts/myofibroblasts at immunofluorescence analysis. The deeper stroma was instead populated by normal stromal cells (i.e., keratocytes). This case report provides the first morphological evidence that persistent SEIs could be the macroscopic expression of subepithelial giant stromal cells with myofibroblast-like characteristics. Such a novel observation might pave the way toward a better targeted therapeutic management of SEIs.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 1","pages":"Article 152231"},"PeriodicalIF":2.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057765","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}