Acta Histochem. [JOURNAL]
Sun
200 papers
Discovery of nuclear cavities in Epstein-Barr virus-infected cells.
Shimada S, Kawasaki H, Katoh H … +1 more , Ishikawa S
Acta Histochem · 2025 Jun · PMID 40253819 · Publisher ↗
Approximately 90 % of humans are infected with the Epstein-Barr virus (EBV); however, most do not develop neoplastic lesions. Despite various investigations, the underlying reasons remain largely unknown. Therefore, we a...
Approximately 90 % of humans are infected with the Epstein-Barr virus (EBV); however, most do not develop neoplastic lesions. Despite various investigations, the underlying reasons remain largely unknown. Therefore, we aimed to address this question through morphological observations to identify the ultrastructural alterations occurring in EBV-infected cells. EBV-positive cells from legacy lymph node specimens obtained from patients with HIV and modern fresh specimens of aberrantly proliferating human EBV-positive lymphocytes in a patient-derived xenograft (PDX) of immunodeficient mouse were examined. By utilizing a special technique that allowed us to observe exactly the same specimen using both optical and electron microscopy, we were able to detect a peculiar phenomenon in EBV-infected cells. EBV-infected lymphocytes occasionally exhibited nuclear cavities, a finding that was confirmed in multiple specimens from both patients with HIV and the PDX model. It was suggested that EBV-infected cells may activate cell death pathways, based on the protein expression patterns of p53 and FAS. Taken together, these results indicated that nuclear cavity formation appeared to be a characteristic morphological alteration associated with EBV infection. Further research could clarify the potential relationship between nuclear cavities and cellular biology in EBV-infected cells, possibly shedding light on the mechanisms that prevent EBV-infected cells from progressing to tumor formation.
Comparison of collagen I and collagen III immunohistochemistry with Herovici staining in various rabbit organs.
Meier Bürgisser G, Giovanoli P, Calcagni M … +1 more , Buschmann J
Acta Histochem · 2025 Jun · PMID 40252250 · Publisher ↗
Collagen I and III distribution is not only crucial to assess the status of healing wounds, but also to characterise healthy connective tissue and pathological extracellular matrix composition. In this technical note, we...
Collagen I and III distribution is not only crucial to assess the status of healing wounds, but also to characterise healthy connective tissue and pathological extracellular matrix composition. In this technical note, we have therefore compared the dual-coloured Herovici staining, indicating pink collagen I and blue collagen III in serial sections with immunohistochemistry (IHC) labellings for collagen I and III, respectively. Furthermore, we used, chromogenic DAB for IHC labelling. Seven different organs of a healthy New Zealand white rabbit were collected for this purpose, including kidney, liver, tonsil, tongue, duodenum, heart, and brain, respectively. A dual-coloured staining like Herovici turned out to be as good as two single-colour labellings utilising IHC. In some cases, co-localisation and extent of collagen I and III expression could be qualitatively visualised better using Herovici, with gradients of blue-violet-pink, than by mere comparison of labelling intensities side by side in two different sections, although taken at the same place as serial sections. Nevertheless, a quantitative analysis of the Collagen I-to-III ratio revealed no significant differences between these two approaches to assess the extracellular matrix composition. From these comparisons, we conclude that a Herovici staining is recommended as a valuable alternative staining to collagen I and III IHC; and it may act as a fast and cheap preliminary staining method. These findings encourage researchers focusing on ECM composition of the experimental rabbit tissue to use Herovici staining to determine the ratio of the extracellular collagen I and III expression.
Fluorescent strategy for detection of uracil-DNA glycosylase activity based on isothermal amplification triggered by ligase.
Zhang P, He F, Chang X … +1 more , Ren C
Acta Histochem · 2025 Jun · PMID 40245473 · Publisher ↗
Uracil-DNA glycosylase (UDG) plays a key role in the base repair system, and detecting its enzymatic activity is crucial for early disease diagnosis. A rapid method for detecting UDG was developed, utilizing amplificatio...
Uracil-DNA glycosylase (UDG) plays a key role in the base repair system, and detecting its enzymatic activity is crucial for early disease diagnosis. A rapid method for detecting UDG was developed, utilizing amplification initiated by a ligation reaction. A DNA probe modified with uracil was utilized to ligate two free DNA strands to form a newly generated DNA strand. This triggers a nicking enzyme-assisted amplification reaction, resulting in the production of single-stranded DNA (ssDNA). Then, the amplified ssDNA triggered the molecular beacons to emit fluorescence. However, the addition of UDG results in the removal of uracil from the DNA probe strand, leaving abasic site (AP site). After heat denaturation, this site was destroyed, preventing subsequent ligation or amplification reactions, resulting in the absence of fluorescence. The findings of our study indicate that the addition of UDG at concentrations exceeding 0.5 U/mL resulted in complete suppression of fluorescence intensity, reaching a value of 0. Conversely, in the absence of the UDG enzyme or upon the addition of other enzymes and proteins such as HAAG, EndoIV and BSA, the fluorescence intensity of the system remains unaffected, achieving 100 % intensity within 5-20 min. This study presents a rapid method for assessing UDG activity that could be valuable for early disease diagnosis in the future.
Immunohistochemistry and machine learning study of DNA replication-associated proteins in uterine epithelial tumors and precursor lesions.
Urata T, Kimura F, Ohshima K … +3 more , Ikehata K, Yamaguchi M, Ishii K
Acta Histochem · 2025 Jun · PMID 40220589 · Publisher ↗
Endometrioid adenocarcinoma (EA) has been on the increase in recent years in developed countries. Early detection of endometrioid adenocarcinoma in the endometrial corpus is crucial for patient prognosis and early treatm...
Endometrioid adenocarcinoma (EA) has been on the increase in recent years in developed countries. Early detection of endometrioid adenocarcinoma in the endometrial corpus is crucial for patient prognosis and early treatment, although their distinction can sometimes be challenging. In this study, we focused on DNA replication-related proteins through immunohistochemical analysis and investigated whether the discrimination between EA and their precursor lesions is achievable using machine learning techniques. The research utilized tissue specimens from 100 cases, including EA of different grades (Grade 1; G1, Grade 2; G2, Grade 3; G3) and their precursor lesions (endometrial hyperplasia without atypia; EH, endometrial atypical hyperplasia: AH). Immunohistochemical analysis of DNA replication-related proteins, such as ORC1, Cdt1, Cdc6, MCM7, Cdc7, and Geminin, was conducted for each case, measuring the Labeling Index (LI) and optical density (OD) of protein expression. Furthermore, we performed statistical significance tests and machine learning -discriminant analysis using LI and OD as inputs, employing non-linear Support Vector Machines (NSVM). The NSVM discriminant analysis demonstrated the accuracy of over 85 % between EH and each differentiation grade of EA, the accuracy is also similar for AH and each differentiation grade of EA. In addition, changing the combination of DNA replication-related proteins used for discrimination resulted in a high accuracy (95-100 %). A discriminant analysis with NSVM using the LI and OD of DNA replication-related proteins may enable the differentiation of EA from its precursor lesions.
Galactia lindenii lectin type-II: Its potential use in thyroid cancer diagnosis.
Cortázar TM, Vega NA, Acosta J … +3 more , Reyes-Montaño EA, Ballen-Vanegas MA, Ricaurte O
Acta Histochem · 2025 Jun · PMID 40188650 · Publisher ↗
Galactia lindenii lectin type-II (GLL-II) belongs to the group of the legume lectins. The present study investigated the GLL-II staining patterns in histological sections of neoplastic and non-neoplastic thyroid tissues....
Galactia lindenii lectin type-II (GLL-II) belongs to the group of the legume lectins. The present study investigated the GLL-II staining patterns in histological sections of neoplastic and non-neoplastic thyroid tissues. Besides, hemagglutination assays (HA) using the GLL-II on red blood cells of different glycomic profiles were performed, complementing previous results. The differential staining in Papillary Thyroid Cancer, Invasive Encapsulated Follicular Variant Papillary Thyroid Carcinoma, Hashimoto's thyroiditis, and non-neoplastic thyroid with goiter changes, together with the HA results, allowed us to propose the potential utility of GLL-II as part of lectin platforms used to discriminate between human thyroid pathological samples from normal ones. The present study shed light on potential applications of GLL-II in determining alterations of glycosylation patterns in specific cells, tissues, or body fluids, as well as glycotopes biomarkers of healthy or pathological conditions.
Silencing Livin gene expression by RNA interference enhanced the chemotherapeutic sensitivity of drug-resistant osteosarcoma cells to doxorubicin.
Huang L, Zeng X, Xiao K … +2 more , Tang S, Sun K
Acta Histochem · 2025 Jun · PMID 40121921 · Publisher ↗
BACKGROUND: 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...
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
The significance of Itga8 and Vangl2 in kidney development: Insights from yotari mice.
Pavlović N, Kelam N, Racetin A … +5 more , Gelemanović A, Filipović N, Bajt P, Katsuyama Y, Vukojević K
Acta Histochem · 2025 Jun · PMID 40101650 · Publisher ↗
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 diagno...
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 yotari (yot) mouse model, which harbors a mutation in the Dab1 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 yot 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 yot mice. Our findings suggest that the Dab1 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.
Exploring the potential of stem cell therapy: Applications, types, and future directions.
Boopathy K, Palaniyandi T, Ravi M … +5 more , Wahab MRA, Baskar G, Rab SO, Saeed M, Balaramnavar VM
Acta Histochem · 2025 Jun · PMID 40020616 · Publisher ↗
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 therapeut...
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.
EFNA1 promotes the tumorigenesis and metastasis of cervical cancer by phosphorylation pathway and epithelial-mesenchymal transition.
Dong X, Chen X, Xue M … +2 more , Zhang Y, Jiang P
Acta Histochem · 2025 Jun · PMID 39999525 · Publisher ↗
BACKGROUND: 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...
BACKGROUND: 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. METHODS: 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 in vitro and in vivo. RESULTS: 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 in vitro and in vivo, inhibiting EMT and MAPK pathways. CONCLUSION: This study revealed the key signaling pathways in CC progression and identified EFNA1 as a crucial prognostic biomarker, potentially impacting CC treatment.
Mechanoresponsive patterns of KLF2, 4, 5, and 6 expression differ among subclones from a single mammary tumor.
Pimenta RML, Skon-Hegg C, Rose-Hellekant T … +1 more , Holy J
Acta Histochem · 2025 Jun · PMID 39983249 · Publisher ↗
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 thei...
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.
Aberration of CA3 functionally mediates the pathogenesis of Cardiomyocyte hypertrophy in a miR-138-5p dependent manner.
Chu T, Han Q, Shi H … +5 more , Li C, Ma Q, Li P, Wang F, Zhang J
Acta Histochem · 2025 Mar · PMID 39923530 · Publisher ↗
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...
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.
Effect of chloroquine on autophagy and the severity of caerulein-induced acute pancreatitis in mice.
Sharma MK, Priyam K, Kumar P … +3 more , Garg PK, Roy TS, Jacob TG
Acta Histochem · 2025 Mar · PMID 39913992 · Publisher ↗
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 fl...
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 CO-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 < 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 < 0.001). Expression of HMGB1was more in group 4 than 3 (p = 0.046). Chloroquine enhances necrosis and inflammation in caerulein-induced pancreatitis.
Spatiotemporal distribution of Wnt signaling pathway markers in human congenital anomalies of kidney and urinary tract.
Perutina I, Kelam N, Maglica M … +9 more , Racetin A, Rizikalo A, Filipović N, Prusac IK, Bošnjak M, Mišković J, Kablar B, Ghahramani N, Vukojević K
Acta Histochem · 2025 Mar · PMID 39908631 · Publisher ↗
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...
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.
3D examination reveals increased destruction of alpha-actin-positive structures in advanced follicular lymphoma stages.
Geib K, Scharf S, Schäfer H … +3 more , Hartmann S, Hansmann ML, Wurzel P
Acta Histochem · 2025 Mar · PMID 39883976 · Publisher ↗
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 met...
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.
New insights into persistent corneal subepithelial infiltrates following epidemic keratoconjunctivitis: The first case report with ultrastructural and immunohistochemical investigations.
Mencucci R, Cennamo M, Rosa I … +5 more , Guasti D, Buzzi M, Sgambati E, Marini M, Manetti M
Acta Histochem · 2025 Mar · PMID 39874705 · Publisher ↗
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 corn...
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.
Normal dermal mesenchymal stem cells improve the functions of psoriatic keratinocytes by inducing autophagy.
Liang N, Cao Y, Li J … +1 more , Zhang K
Acta Histochem · 2025 Mar · PMID 39864345 · Publisher ↗
OBJECTIVE: Psoriasis is a chronic inflammatory skin disease characterized by excessive proliferation and abnormal differentiation of keratinocytes. Although stem cell-based therapies have shown promise in treating psoria...
OBJECTIVE: Psoriasis is a chronic inflammatory skin disease characterized by excessive proliferation and abnormal differentiation of keratinocytes. Although stem cell-based therapies have shown promise in treating psoriasis, the underlying mechanisms remain unclear. This study aimed to established a psoriatic cell model to investigate the effect of normal dermal mesenchymal stem cell (DMSCs) on keratinocyte proliferation, inflammation responses and the associated mechanism. METHODS: To create an in vitro model of psoriasis, HaCaT cells were stimulated with a mixture of five inflammatory cytokines including IL-17A, IL-22, oncostatin M, IL-1α, and TNF-α (M5). A transwell co-culture system was employed to assess the influence of normal DMSCs on proliferation and inflammation response of HaCaT cells. Cell viability was assessed using the CCK-8 assay and EDU incorporation assay. The expression levels of mRNA for inflammatory cytokines (IL-8, IL-17A and TNF-α) in HaCaT cells co-cultured with either normal or psoriatic DMSCs were quantified by qRT-PCR. Apoptosis was evaluated by annexin V-FITC/PI double staining and TUNEL/DAPI staining assay. Autophagy was detected by immunostaining, RT-PCR and western blotting. Additionally, the expression levels of mRNA and protein of both Akt and mammalin target of rapamycin(mTOR) were also determined. RESULTS: Normal DMSCs were found to decrease the viability and promote apoptosis of HaCaT cells treated with M5. Furthermore, DMSCs reduced the secretion of proinflammatory cytokines, such as IL-8, IL-17A and TNF-α. Importantly, normal DMSCs were shown to induced autophagy in HaCaT cell. Pretreatment of HaCaT cells with autophagy inhibitor 3-methyladenine (3-MA) reversed the anti-psoriatic effect of normal DMSCs. Notably, DMSCs promote autophagy in M5-treated HaCaT cells by inhibition of p-Akt/Akt and p-mTOR/mTOR ratio. CONCLUSION: Normal mesenchymal stem cells promote autophagy through the inhibition of Akt/mTOR signaling pathway, leading to the alleviation of psoriasis in vitro. These findings provide insights into the potential mechanisms by which DMSCs may exert therapeutic effects in psoriasis and support further investigation into their clinical applications.
SOX2 promotes the glycolysis process to accelerate cervical cancer progression by regulating the expression of HK2.
Wang T, Jiang R, Tang X … +2 more , Yao Y, Jiang P
Acta Histochem · 2025 Mar · PMID 39823909 · Publisher ↗
BACKGROUND: Cervical cancer is a major health burden in females worldwide, available studies indicated that sex-determining region Y-box 2 (SOX2) is closely related to the malignant phenotypes of multiple cancers includi...
BACKGROUND: Cervical cancer is a major health burden in females worldwide, available studies indicated that sex-determining region Y-box 2 (SOX2) is closely related to the malignant phenotypes of multiple cancers including cervical cancer. However, the underlying mechanisms were blurred. EXPERIMENTAL PROCEDURES: A bioinformatics analysis was conducted to investigate the clinical correlation between SOX2 and cervical cancer. Transient transfection and lentivirus infection were utilized to achieve overexpression and knockdown of SOX2, respectively. The role of SOX2 in cervical cancer was confirmed by transwell and colony-forming assays. Immunoblot, dual-luciferase reporter, chromatin immunoprecipitation (ChIP), and biochemical experiments were employed. In addition, the xenograft models and immunohistochemistry (IHC) experiments were performed to validate the findings in vivo. RESULTS: The expression of SOX2 was significantly positively associated with the cell migration, invasion, and colony-forming abilities of cervical cancer cells. The following immunoblots revealed that the SOX2-induced malignant phenotypes might be related to the glycolysis process, since overexpressing SOX2 significantly promoted the hexokinase 2 (HK2) and glucose transporter-1 (GLUT1) expression, and increased the content of glucose and lactic acid. The further dual-luciferase reporter and ChIP experiments confirmed a binding relationship between SOX2 and HK2 promoter. More importantly, overexpressing SOX2 promoted tumor growth concomitant with a hyper-expression of HK2 and GLUT1 in xenograft tumor tissues, yet the treatment of glycolysis inhibitor significantly reversed those outcomes. CONCLUSION: SOX2 promotes the malignant progression of cervical cancer by facilitating glycolysis.
Prebiotic RNA self-assembling and the origin of life: Mechanistic and molecular modeling rationale for explaining the prebiotic origin and replication of RNA.
Stockert JC, Horobin RW
Acta Histochem · 2025 Mar · PMID 39788859 · Publisher ↗
In recent years, a great interest has been focused on the prebiotic origin of nucleic acids and life on Earth. An attractive idea is that life was initially based on an autocatalytic and autoreplicative RNA (the RNA-worl...
In recent years, a great interest has been focused on the prebiotic origin of nucleic acids and life on Earth. An attractive idea is that life was initially based on an autocatalytic and autoreplicative RNA (the RNA-world). RNA duplexes are right-handed helical chains with antiparallel orientation, but the rationale for these features is not yet known. An antiparallel (inverted) stacking of purine nucleosides was reported in crystallographic studies. Molecular modeling also supports the inverted orientation of nucleosides. This preferential stacking can also appear when nucleosides are included in a montmorillonite clay matrix. Free-energy values and geometrical parameters show that D-ribose chirality is preferred for the formation of right-handed RNA molecules. Thus, a "zipper" model with antiparallel and auto-intercalated nucleosides linked by phosphate groups can be proposed to form single RNA chains. Unstacking with strand separation and base pairing by H-bonding, results in shortening and inclination of ribose-phosphate chains, leading to right-handed helicity and antiparallel duplexes. Incorporation of complementary precursors on the major groove template by a self-assembly mechanism provides a prebiotic (non-enzymatic) "tetris" replication model by formation of a transient RNA tetrad and tetraplex. Original hairpin motifs appear as simple building units that form typical RNA structures such as hammerheads, cloverleaves and dumbbells. They occur today in the circular viroids and virusoids, as well as in highly branched and complex rRNA molecules.
Angiopoietins/Tie2 signaling axis and its role in angiogenesis of psoriasis.
Li J, Hou H, Li J … +1 more , Zhang K
Acta Histochem · 2025 Mar · PMID 39752990 · Publisher ↗
Hyperplasia of microvessels in the superficial dermis is the main pathological feature of psoriasis, and is linked to the pathogenesis of psoriasis. Thus, anti-angiogenic therapy may be effective for psoriasis. Angiopoie...
Hyperplasia of microvessels in the superficial dermis is the main pathological feature of psoriasis, and is linked to the pathogenesis of psoriasis. Thus, anti-angiogenic therapy may be effective for psoriasis. Angiopoietins (Angs) are crucial angiogenic factors. Ang1 supports a static mature vascular phenotype, while Ang2 is associated with the formation of abnormal vascular structure, vascular leakage and inflammation. The Ang/Tie2 axis and its signal transduction play an important role in regulation of vascular stability, angiogenesis and inflammation. Targeting the Ang/Tie2 signal axis can normalize microvessels in psoriatic lesions. This paper reviews Ang/Tie2 signal axis and its role in angiogenesis of psoriasis, aiming to provide new ideas and strategies for anti-angiogenic therapy of psoriasis.
Acridine orange fluorescence in chromosome cytochemistry: Molecular modeling rationale for understanding the differential fluorescence on double- and single-stranded nucleic acids.
Blázquez-Castro A, Stockert JC
Acta Histochem · 2025 Mar · PMID 39709750 · Publisher ↗
Many fluorophores display interesting features that make them useful biological labels and dyes, particularly in Cell Biology and Cytogenetics. Changes in the absorption-emission spectra (ortho- and metachromasia) are ac...
Many fluorophores display interesting features that make them useful biological labels and dyes, particularly in Cell Biology and Cytogenetics. Changes in the absorption-emission spectra (ortho- and metachromasia) are accounted among them. Acridine orange (AO) is one of such fluorochromes with an exemplary orthochromatic vs. metachromatic emission, which depends on its concentration and binding mode to different cell substrates. Here, we revisit the differential AO fluorescence that occurs in selected biological materials, which allows the identification of single-stranded or double-stranded nucleic acids. Although known for a long time, the ultimate reason for this differential phenomenon has not been properly addressed. We propose a potential molecular mechanism that adequately accounts for the distinct AO emission when bound either to denatured or denatured-reassociated DNA. This mechanism, based on theoretical molecular modelling, implies a difference in the degree of overlap of excited state orbitals whenever AO molecules are interacting with bases from single- or double-stranded nucleic acids. In the first case, massive orbital overlapping leads to a metachromatic red AO emission. Otherwise, no excited-state orbital overlapping occurs, due to excessive distance between intercalated AO molecules, which manifests as orthochromatic green fluorescence. Our molecular modelling supports this interplay between orbital overlap/not overlap and metachromatic/orthochromatic fluorescence.
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