European Journal Of Histochemistry[JOURNAL]
Sun
200 papers
Downregulation of GMPS inhibited the proliferation of hepatocellular cancer cells the regulation of STAT3/c-Myc pathway.
Guo Z, Yu J, Sun J … +2 more , Yang S, Pu J
Eur J Histochem · 2026 Apr · PMID 42294982 · Publisher ↗
Hepatocellular cancer (HCC) is the sixth most common type of cancer worldwide. Guanosine monophosphate synthase (GMPS) participates in the regulation of chromatin and genes in various organisms, and is highly expressed i...
Hepatocellular cancer (HCC) is the sixth most common type of cancer worldwide. Guanosine monophosphate synthase (GMPS) participates in the regulation of chromatin and genes in various organisms, and is highly expressed in a number of human malignant tumors. However, the role of GMPS in HCC has not yet been fully studied and clarified. In this study, the differential fold changes in gene expression levels between HCC cancer tissues and correspondent adjacent normal tissue in The Cancer Genome Atlas Program and GEO datasets were analyzed using R language. GMPS expression levels in HCC cells were knocked down using specific siRNAs. In addition, CCK-8, EdU, TUNEL and immunofluorescence staining were conducted to explore the effects of GMPS siRNAs on HCC cell viability, proliferation, apoptosis and the STAT pathway level, respectively. The results indicated GMPS expression was significantly increased in HCC tumor tissues compared with the corresponding adjacent normal tissues. In addition, high expression of GMPS is negatively associated with the survival rate of patients with HCC. In vitro studies illustrated the knockdown of GMPS notably prevented HCC cell proliferation and induced HCC cell (Hep3B2.1-7 and MHCC97H) apoptosis by regulating the STAT3/c-Myc pathway. The apoptosis-specific marker cleaved caspase was significantly upregulated by GMPS knockdown in HCC cells. The findings of the present study revealed the association between GMPS and the prognosis of HCC. The results suggested that GMPS may serve as a promising marker for the prognosis of HCC, and it may also be a potential therapeutic target for HCC. These findings may lay the theoretical foundation for the clinical application of GMPS.
Histochemical characterization of TDAG51 in endothelial remodeling and angiogenesis following myocardial infarction PI3K-AKT signaling.
Liu K, Pan J, Liu Q … +6 more , Huang Y, Shang L, Zhang Y, Wen J, Li H, Wu Z
Eur J Histochem · 2026 Apr · PMID 42294796 · Publisher ↗
Myocardial infarction (MI) triggers complex cardiac remodeling, including endothelial dysfunction, fibrosis, and angiogenesis. Characterizing the spatial distribution and cellular localization of regulatory molecules is...
Myocardial infarction (MI) triggers complex cardiac remodeling, including endothelial dysfunction, fibrosis, and angiogenesis. Characterizing the spatial distribution and cellular localization of regulatory molecules is critical for understanding cardiac repair mechanisms. This study investigated the histochemical localization and functional role of T-cell death-associated gene 51 (TDAG51) in endothelial cells during post-MI angiogenesis and cardiac remodeling. We established a murine MI model and silenced TDAG51 with adeno-associated virus. Histochemical assays were used to determine TDAG51 localization and its relation to vascular density, and Masson staining was used to evaluate myocardial fibrosis. In vitro, we exposed human coronary artery endothelial cells (HCAECs) to oxygen-glucose deprivation (OGD) to examine TDAG51 expression and endothelial function. We performed Western blot and transcriptomic analyses to explore the involvement of the PI3K-AKT signaling pathway. Histochemical analyses revealed that TDAG51 was predominantly localized in CD31-positive endothelial cells and was significantly upregulated in the infarcted myocardium, particularly in the peri-infarct regions. TDAG51 silencing markedly increased capillary density and reduced fibrotic area, as demonstrated by immunohistochemistry and Masson staining. In vitro, TDAG51 knockdown enhanced endothelial proliferation, migration, and tube formation. Mechanistically, these effects were associated with activation of the PI3K-AKT signaling pathway, while pharmacological inhibition of PI3K attenuated the pro-angiogenic phenotype. This study provides histochemical evidence that TDAG51 is enriched in ischemic myocardial endothelial cells and negatively regulates angiogenesis. TDAG51 inhibition promotes vascular remodeling and enhances cardiac repair following myocardial infarction, highlighting TDAG51 as a promising therapeutic target for improving post-MI recovery.
Elevated caspase 3 expression correlates with severe inflammation in Crohn's disease.
Sejdiu N, Naumann M, Vieth M
Eur J Histochem · 2026 Apr · PMID 42233876 · Full text
Caspase 3 is a key executioner of apoptotic cell death and contributes to intestinal epithelial homeodynamics. Apoptotic dysregulation has been implicated in Crohn's disease, yet data on caspase 3 expression across disea...
Caspase 3 is a key executioner of apoptotic cell death and contributes to intestinal epithelial homeodynamics. Apoptotic dysregulation has been implicated in Crohn's disease, yet data on caspase 3 expression across disease activity states remain limited. This study analyzed caspase 3 expression in intestinal biopsies from Crohn's disease patients. Paraffin-embedded biopsies from 289 individuals were examined, including active disease (mild and severe inflammation), upper gastrointestinal involvement, remission and non-inflamed tissue. Expression in epithelial and immune cells was assessed by immunohistochemistry and scored using the Remmele immunoreactive score (IRS). Caspase 3 expression levels in epithelial cells increased in cases of severe inflammation (p=0.012), and immune cells exhibited even more pronounced expression levels (p<0.001). These findings suggest that caspase 3 expression in epithelial and immune cells may help to distinguish between mild and severe inflammation.
Astragaloside IV inhibits nasopharyngeal carcinoma progression by inhibiting SATB2/Wnt/PD-L1 pathway and enhancing the killing activity of T cells.
Zeng Y, Huang J, Duan T … +1 more , Wang X
Eur J Histochem · 2026 Apr · PMID 42206678 · Full text
Astragaloside IV (AS IV) inhibits the malignant phenotype of nasopharyngeal carcinoma (NPC), but whether its mechanism involves the regulation of immune checkpoint programmed cell death-ligand 1 (PD-L1) is not clear. Hum...
Astragaloside IV (AS IV) inhibits the malignant phenotype of nasopharyngeal carcinoma (NPC), but whether its mechanism involves the regulation of immune checkpoint programmed cell death-ligand 1 (PD-L1) is not clear. Human NPC cells were treated with AS IV. The effects of AS IV on PD-L1 expression were assessed using RT-qPCR and Western blot. SATB2/Wnt/β-catenin signaling axis regulation was analyzed by siRNA interference, plasmid overexpression and Wnt pathway inhibitor DKK-1. T cell killing activity and tumor malignant phenotype were evaluated by LDH release, ELISA, flow cytometry and Transwell experiments. huHSC-NCG tumor-bearing mice were established to detect tumor growth, immune cell infiltration and related protein expression. AS IV dose-dependently inhibited PD-L1 expressions within NPC cells, and enhanced the activation and killing function of CD8+ T cells. Mechanism studies have shown that AS IV significantly lowered the expression of SATB2, thereby inhibiting Wnt/β-catenin axis and c-MYC and Axin2 expressions, and ultimately reducing PD-L1 levels. Overexpression of SATB2 reversed AS IV's suppression of this signaling and PD-L1. Animal experiments confirmed that AS IV effectively inhibited tumor growth, enhanced CD8+ T cell infiltration and activity within tumor tissues, and down-regulated the SATB2/β-catenin/PD-L1 signal axis. AS IV inhibited PD-L1 expression in NPC via targeting the SATB2/Wnt/β-catenin axis, thereby activating CD8+ T cells, amplifying immunological responses, and ultimately inhibiting NPC growth. Graphical Abstract.
SUSD2 suppresses lung adenocarcinoma tumorigenesis by inducing autophagy inhibiting PI3K/AKT/mTOR signaling pathway.
Wang S, Yang G, Zhang Q … +1 more , Zhang Y
Eur J Histochem · 2026 Apr · PMID 42148660 · Full text
Lung adenocarcinoma (LUAD) is the most common and aggressive non-small cell lung cancer with limited therapeutic options. SUSD2 exhibits varying regulatory behaviors in different types of tumors, its role in LUAD remains...
Lung adenocarcinoma (LUAD) is the most common and aggressive non-small cell lung cancer with limited therapeutic options. SUSD2 exhibits varying regulatory behaviors in different types of tumors, its role in LUAD remains unclear. This study aims to determine the role of SUSD2 in LUAD and explore the underlying mechanism. Through TCGA database analysis, we discovered that SUSD2 expression is significantly downregulated in LUAD tissues, and its low expression is closely associated with advanced disease stages and poor patient prognosis. Further immunohistochemical validation confirmed reduced SUSD2 expression in clinical samples. Functional assays demonstrated that SUSD2 overexpression markedly inhibits LUAD cell proliferation, migration, and invasion, and also suppresses tumor growth and metastasis in mouse models. Mechanistic studies revealed that SUSD2 overexpression promotes autophagic flux (indicated by increased LC3-II and decreased p62) and suppresses the PI3K/AKT/mTOR signaling pathway. The antitumor effects of SUSD2 were attenuated by the autophagy inhibitor 3-MA or ATG5 knockdown, while reactivation of mTOR reversed SUSD2-induced autophagy and tumor suppression. In summary, SUSD2 functions as a tumor suppressor in LUAD by inducing autophagy and inhibiting the PI3K/AKT/mTOR pathway, suggesting its potential as a therapeutic target and prognostic biomarker.
Colchicine alleviates severe acute pancreatitis in rats by inhibiting acinar cell ferroptosis LCN2/MAPK/ERK signaling axis.
Yang L, Zheng X, Zhang Y … +3 more , Li Y, Li L, Liu F
Eur J Histochem · 2026 Apr · PMID 42112745 · Full text
Colchicine (COL) is known to ameliorate severe acute pancreatitis (SAP), yet the precise molecular mechanisms remain elusive. This study integrates bioinformatics with in vivo experimentation to elucidate the mechanism b...
Colchicine (COL) is known to ameliorate severe acute pancreatitis (SAP), yet the precise molecular mechanisms remain elusive. This study integrates bioinformatics with in vivo experimentation to elucidate the mechanism by which COL attenuates SAP. An SAP rat model was established via sodium taurocholate injection. Key therapeutic targets were screened using transcriptomics and network pharmacology. Mechanistic validation utilized AAV-mediated lipocalin-2 (LCN2) overexpression, the ferroptosis inhibitor ferrostatin-1 (Fer-1), and the ERK inhibitor PD98059. COL treatment significantly ameliorated pancreatic pathological injury, inflammatory cell infiltration, and cytokine release. LCN2 was identified as a pivotal target markedly upregulated in SAP but downregulated by COL. Crucially, LCN2 overexpression reversed COL's therapeutic benefits and restored ferroptosis markers (COX2, Fe2+, ROS) while suppressing anti-ferroptotic indices. Notably, this reversal was effectively abrogated by co-treatment with either Fer-1 or PD98059, confirming the involvement of the MAPK/ERK pathway. This study is the first to elucidate that COL inhibits ferroptosis in pancreatic acinar cells by downregulating LCN2 and subsequently suppressing the LCN2/MAPK/ERK signaling axis. These findings provide a novel molecular basis for COL and highlight a potential target for therapeutic intervention in SAP.
Senolytics alleviate cyclophosphamide-induced premature ovarian insufficiency by eliminating senescent cells.
Su H, Ma R, Su D … +3 more , Tan C, Zhu Y, Yang X
Eur J Histochem · 2026 Apr · PMID 42011821 · Full text
Alkylating agents, particularly cyclophosphamide (CY), are known for their high toxicity, which can lead to iatrogenic premature ovarian insufficiency (POI) and infertility in young cancer survivors. Currently, effective...
Alkylating agents, particularly cyclophosphamide (CY), are known for their high toxicity, which can lead to iatrogenic premature ovarian insufficiency (POI) and infertility in young cancer survivors. Currently, effective prevention and treatment strategies remain limited. Given that chemotherapy induces cellular senescence, we investigated the therapeutic potential of dasatinib (D) and quercetin (Q), a senolytic combination known to eliminate senescent cells. Using a CY-induced murine model of ovarian injury, we found that CY treatment increased the accumulation of senescent cells in the ovaries. The resulting senescence-associated secretory phenotype (SASP) led to a deterioration of the ovarian microenvironment, characterized by increased follicular atresia and a decline in follicle quantity, ultimately culminating in POI. Our findings demonstrate that DQ therapy effectively mitigated CY-induced damage by clearing senescent cells and reducing SASP secretion. Clinically, DQ administration restored sex hormone levels and regularity of the estrous cycle, resulting in an overall increase in follicle numbers across all developmental stages. Furthermore, DQ treatment significantly normalized estrous cyclicity, restoring regular cycles in 60% of the CY+DQ mice compared to only ~15% in the CY-alone group (p<0.0001). RNA sequencing analysis revealed that DQ treatment upregulated Pagr1a, a gene associated with extraembryonic development, while downregulating genes involved in senescence induction (Itgb3, Wnt10b, Vegfa) and immune function (A2m, Ccl21d). These results suggest that senescent cells drive CY-induced ovarian damage and that DQ represents a promising therapeutic strategy for preserving the ovarian reserve and endocrine function in female cancer patients.
Ketogenic diet regulates Uch-L1(C) to improve cerebral energy metabolism and cognitive function in Alzheimer's disease mice.
Bao N, Zhang M, Tang M … +3 more , Shen Z, Wang S, Jiang G
Eur J Histochem · 2026 Apr · PMID 42007524 · Full text
The ketogenic diet (KD), a high-fat, low-carbohydrate diet, can effectively regulate energy metabolism in the brain. The regulation of cerebral energy metabolism in patients with Alzheimer's disease (AD) has attracted th...
The ketogenic diet (KD), a high-fat, low-carbohydrate diet, can effectively regulate energy metabolism in the brain. The regulation of cerebral energy metabolism in patients with Alzheimer's disease (AD) has attracted the attention of researchers. Recent studies have shown that ubiquitin carboxyl terminal hydrolase L1 (Uch-L1) deficiency leads to neurodegeneration by increasing energy demand and endoplasmic reticulum stress. However, the effect of Uch-L1 on AD remains to be explored. This study first combined Uch-L1 with cerebral energy metabolism to explore its role in long-term KD in AD. We found that AD mice with long-term KD showed better spatial recognition and working memory. KD promoted Uch-L1(C) and Mfn2 expression by inhibiting oxidative stress in the hippocampus of mice, improved mitochondrial function, increased ATP content, and significantly reduced neuronal apoptosis. In conclusion, KD can increase Uch-L1(C) and Mfn2 expression in the brain, and improve cerebral energy metabolism and cognitive function in AD mice.
Electroacupuncture combined with rTMS promotes neuronal regeneration DNMT1-mediated PI3K-AKT pathway in cerebral palsy model.
Fan J, Ma Y, Sun L … +2 more , Miao S, He J
Eur J Histochem · 2026 Apr · PMID 42007516 · Full text
Cerebral palsy (CP), resulting from perinatal brain injury, is characterized by persistent motor dysfunction largely due to impaired regeneration of the corticospinal tract. Electroacupuncture (EA) and repetitive transcr...
Cerebral palsy (CP), resulting from perinatal brain injury, is characterized by persistent motor dysfunction largely due to impaired regeneration of the corticospinal tract. Electroacupuncture (EA) and repetitive transcranial magnetic stimulation (rTMS) are promising non-invasive neuromodulation approaches, but their combined effects and epigenetic mechanisms remain unclear. This study examined the synergistic neurorestorative potential of EA and rTMS in a hypoxic-ischemic brain damage (HIBD) model of CP, focusing on DNA methyltransferase 1 (DNMT1) regulation of the PI3K-AKT pathway. In vivo, neonatal rats subjected to HIBD were assigned to control, HIBD, EA, rTMS, or combined EA+rTMS groups and treated for four weeks. Motor function was assessed using rotarod, grid-walking, and grip strength tests, while neuronal and molecular changes were analyzed via histological and biochemical methods. In vitro, hypoxia-exposed cortical neurons underwent DNMT1 and PI3K modulation to clarify mechanisms. Combined EA+rTMS produced superior functional recovery compared to monotherapies, including a 2.1-fold increase in rotarod latency, 53% reduction in foot faults, and 80% improvement in grip strength vs untreated HIBD animals. Improvements were also greater than EA or rTMS alone. Histological findings showed enhanced neuronal density in cortical and spinal regions. At the molecular level, combined treatment suppressed DNMT1 expression and increased PI3K, phosphorylated AKT, GAP-43, and myelin basic protein. In vitro, DNMT1 knockdown enhanced PI3K-AKT signaling, neuronal survival, and axonal growth, while DNMT1 overexpression or PI3K inhibition negated these effects. Overall, EA+rTMS promotes functional and structural recovery in CP by epigenetically inhibiting DNMT1 and activating the PI3K-AKT pathway, supporting its translational potential for perinatal brain injury.
Back to the future: improving storage of Golgi-stained mouse brain.
De Luca F
Eur J Histochem · 2026 Jan · PMID 41784050 · Full text
Morphological analysis of neuronal processes and their networks is a key aspect of neuroscience, with relevance from basic research to clinical practice due to the central role of neuronal development and plasticity in m...
Morphological analysis of neuronal processes and their networks is a key aspect of neuroscience, with relevance from basic research to clinical practice due to the central role of neuronal development and plasticity in many neurological disorders. More than a century after its introduction, Golgi staining, a technique based on the random precipitation of metallic deposits in different neuronal subtypes, remains a highly valuable method for investigating the cellular morphology of neurons in the nervous system. Despite the wide range of protocols developed over the years, several limitations of the technique remain a matter of discussion. Among these is the need to extend sample preservation during the interval between staining and sectioning procedures without compromising the quality of the histochemical labeling. By adopting a specific processing method, the present study demonstrates that it is possible to embed murine nervous tissue following Golgi staining and to preserve the samples for extended periods prior to sectioning, while maintaining well-preserved and clearly detectable histochemical labeling across different regions and neurons of the mouse central nervous system.
SRSF3 promotes the generation of XBP1s to stabilize autophagy and enhance hypoxia adaptation in glioma.
Liu B, Zhang X, Tian J … +5 more , Huang X, Li X, Zhao J, Xu Z, Pu J
Eur J Histochem · 2026 Jan · PMID 41778901 · Full text
Hypoxia is a key driver of glioblastoma (GBM) progression. Serine/arginine-rich splicing factor 3 (SRSF3) is associated with the malignant progression of GBM, but its role in the hypoxic microenvironment of GBM remains u...
Hypoxia is a key driver of glioblastoma (GBM) progression. Serine/arginine-rich splicing factor 3 (SRSF3) is associated with the malignant progression of GBM, but its role in the hypoxic microenvironment of GBM remains unclear. This study aimed to explore the regulatory role and molecular mechanisms of SRSF3 in hypoxia adaptation in GBM. The expression of SRSF3 in normal astrocytes and GBM cells was detected. The effects of knockdown or overexpression of SRSF3 combined with hypoxia treatment on malignant phenotypes and hypoxia stress adaptation in GBM cells were evaluated. Cell viability, colony formation, migration, invasion, and cell death assays were performed to assess phenotypic changes. Mechanisms were investigated using mRFP-GFP-LC3, autophagy, and unfolded protein response (UPR)-related molecular detection. SRSF3 was highly expressed in GBM cells. Knockdown of SRSF3 inhibited cell viability, migration, invasion, and colony formation, whereas overexpression of SRSF3 promoted malignant behaviors. Further studies revealed that hypoxia induction significantly increased the expression levels of GRP78, CHOP, ATF4, LC3-II/I, and p62; upregulated the GFP/mRFP ratio; and increased cleaved-caspase3 expression, promoting cell death. Mechanistic studies revealed that SRSF3 overexpression promoted XBP1s formation, alleviated hypoxia-induced autophagic flux blockage, and reduced cell death. The IRE1 RNase inhibitor 4μ8C weakened the SRSF3-mediated promotion of XBP1s generation. SRSF3 enhances adaptive UPR output by promoting IRE1-dependent XBP1 splicing, thereby maintaining autophagic flux and promoting GBM cell survival under hypoxic conditions.
Cryptotanshinone alleviates DSS-induced colitis in mouse by regulating the balance of Treg/Th17 cells and M1 macrophage activation.
Liu L, Huang W, Wu Y … +4 more , Ye G, Zhang J, Shen T, Ouyang C
Eur J Histochem · 2026 Jan · PMID 41711159 · Full text
Inflammatory bowel disease (IBD) including ulcerative colitis (UC) and Crohn's disease has become a global disease in the 21st century, with increasing incidence rates in almost every industrialized country. Previous stu...
Inflammatory bowel disease (IBD) including ulcerative colitis (UC) and Crohn's disease has become a global disease in the 21st century, with increasing incidence rates in almost every industrialized country. Previous studies have suggested that the traditional Chinese medicine herb, cryptotanshinone (CTN), a major liposoluble extract of Salvia miltiorrhiza, alleviates the symptoms of experimental colitis in vitro and in vivo. However, the mechanisms underlying the protective effects of CTN against IBD remain exclusive. The present study found that CTN reversed lipopolysaccharide-induced inflammation in human colon epithelial cells (HIEC-6) by inhibiting the NF-κB pathway. In addition, CTN alleviated dextran sulfate sodium (DSS)-induced inflammatory bowel disease in mice by regulating the balance of TH17/Treg cells. CTN also exerted its role by inhibiting the polarization of M1 macrophages in mice with DSS-induced colitis. Of note, the effects of CTN on these immune cells may be mediated via changes in the levels of TNF-α and IL-6 directly in mice. Taken together, these findings may provide new insight regarding the therapeutic potential of CTN for UC.
Histopathological and immunofluorescent characterization of post-sepsis immune dysregulation in a clinically relevant mouse model.
Tang H, Liao C, Tang N … +4 more , Li H, Liu Y, Wang L, Ren Z
Eur J Histochem · 2026 Jan · PMID 41684325 · Full text
Sepsis remains a major cause of morbidity and mortality worldwide, yet its prolonged pathophysiological consequences are poorly understood. Here, we employed a murine cecal ligation and puncture (CLP) model to investigat...
Sepsis remains a major cause of morbidity and mortality worldwide, yet its prolonged pathophysiological consequences are poorly understood. Here, we employed a murine cecal ligation and puncture (CLP) model to investigate the prolonged impact of sepsis on survival, systemic inflammation, and organ pathology. Adult male C57BL/6 mice underwent CLP or sham surgery and were monitored for 28 days. Survival was recorded daily, while serial assessments of hematology, serum biochemistry, bacterial load, and cytokine levels were performed. Tissue immunofluorescence was used to characterize myeloid-derived suppressor cells (MDSCs), which are potent immunosuppressive cells that inhibit both adaptive and innate immune responses in sepsis, contributing to sepsis-induced immunosuppression. Histopathological analyses were conducted to evaluate structural changes in major organs. CLP mice displayed markedly reduced long-term survival compared with sham controls. Hematological profiling revealed persistent leukocytosis and an inflammatory response, while serum analyses showed sustained elevations in in bilirubin, creatinine, and blood urea nitrogen, reflecting hepatic and renal injury. Bacterial cultures confirmed systemic microbial persistence, and cytokine measurements indicated ongoing inflammatory activity. Tissue immunofluorescence demonstrated the infiltration of MDSCs across multiple organs, consistent with post-sepsis immunosuppression. Histopathological examination revealed widespread, chronic injury in the lungs, liver, kidneys, and spleen, including inflammatory infiltration, tissue degeneration, and architectural disruption. In conclusion, sepsis induces not only acute systemic inflammation but also enduring immune dysregulation and progressive organ damage. These findings highlight the CLP model as a robust platform for studying post-sepsis sequelae and underscore the need for therapeutic strategies that target long-term organ protection and immune restoration.
Immunohistochemical detection of putative pathogenetic factors in adhesions of infants: a pilot study.
Pauliņš A, Junga A, Pilmane M
Eur J Histochem · 2026 Jan · PMID 41684316 · Full text
Newborns' intestinal adhesions have been reported in 4.7% infants who underwent a laparotomy, but adhesions can also appear idiopathically. Etiology and pathogenesis of adhesions is still to be determined, but evidence s...
Newborns' intestinal adhesions have been reported in 4.7% infants who underwent a laparotomy, but adhesions can also appear idiopathically. Etiology and pathogenesis of adhesions is still to be determined, but evidence shows relation to inflammation, formation of fibrin bands, hypoxia and tissue remodelation. Multiple candidate genes have been associated with adhesion development. The aim of this study was to evaluate the appearance of Sonic Hedgehog (SHH), Indian Hedgehog (IHH), Forkhead-box F1 (FOXF1), caudal type homeobox 1 (CDX1), HCLS1-associated protein X-1 (HAX-1), GATA Binding Protein 4 (GATA4) and Granzyme-B (GZMB) proteins in infant adhesions and to describe possible interfactorial correlations. Adhesion affected tissue samples were collected from 14 patients under one year of age that underwent abdominal surgery to treat partial or complete intestinal obstruction. The control group consisted of 6 individuals that had surgical repairment of inguinal hernia. Routine staining and immunohistochemistry were performed. Immunopositive fibroblasts, macrophages, endotheliocytes, smooth muscle myocytes of blood vessel wall and mesotheliocytes were investigated. The relative distribution of all factors was evaluated by the semiquantitative counting method. Statistical analysis was done using non-parametric tests and correlations were calculated based on Spearman's correlation analysis. A statistically significant decrease was observed for SHH, IHH, FOXF1, GATA4 and partially for GZMB in the adhesion group. There were also decreased HAX-1 and CDX1 immunopositive structures in the adhesion group, however, without any statistical significance. SHH, IHH, FOXF1, GATA4 and GZMB might have a role in adhesion development among infant patients which could suggest a dysregulation of cellular events. Abundance of correlations between the gene protein appearances in different structures indicate the affected blood vessels, fibroblasts and macrophages, however, mesothelium seems not to be the key driver in the morphopathogenesis of adhesion development.
Overexpression of GPER1 suppressed esophageal carcinoma growth activating cAMP pathway.
Yin H, Han X, Zhang Q … +2 more , Li D, Wang F
Eur J Histochem · 2026 Jan · PMID 41586754 · Full text
G protein-coupled estrogen receptor 1 (GPER1) has extensively verified as a tumor regulator in various types of cancers. However, its role in esophageal cancer (EC) remains largely unclear. In this study, the expression...
G protein-coupled estrogen receptor 1 (GPER1) has extensively verified as a tumor regulator in various types of cancers. However, its role in esophageal cancer (EC) remains largely unclear. In this study, the expression and prognostic prediction value of GPER1 in EC was analyzed by using TCGA database and was verified in EC cells and fresh tissues. The results showed that GPER1 is decreased in EC cells and tissues, and lower GPER1 expression is associated with poor overall survival of EC patients. CCK-8 assay and flow apoptosis cytometry were applied to measure the ability of proliferation and apoptosis of EC cells with or without GPER1 overexpression. The levels of reactive oxygen species (ROS) and Fe2+ were determined by flow cytometry. Elisa and Western blotting were employed to measure the markers of ferroptosis and cyclic adenosine monophosphate (cAMP) pathway. The results of in vitro experiments indicated that overexpression of GPER1 caused decreased proliferation, increased cell apoptosis, ROS generation, Fe2+ content and acyl-CoA synthetase long-chain family member 4 (ACSL4) expression, while decreased glutathione peroxidase 4 (GPX4) expression. Notably, the cAMP/PKA inhibitor H89 significantly reversed the ferroptotic effects induced by GPER1, indicating the essential role of the cAMP pathway in this process. The weight and volumes of tumors were measured and Ki-67 and H&E staining were conducted to analyze the effect of GPER1 in vivo. The results of in vivo experiments indicated that overexpression of GPER1 resulted in restricted tumor growth, reduced Ki-67 expression and increased cell death. In conclusion, the expression of GPER1 is reduced in EC. Overexpression of GPER1 enhances ferroptosis in EC, primarily through activation of the cAMP signaling pathway.
Low ozone concentrations promote preservation of explanted articular cartilage: an ultrastructural study.
Remoli G, Inguscio CR, Boschi F … +3 more , Tabaracci G, Malatesta M, Cisterna B
Eur J Histochem · 2026 Jan · PMID 41586752 · Full text
Ozone (O3) is an oxidizing natural gas widely applied as adjunctive therapeutic treatment for a variety of pathological conditions. Currently, O3-based therapies rely on the low-dose concept i.e., the administration of l...
Ozone (O3) is an oxidizing natural gas widely applied as adjunctive therapeutic treatment for a variety of pathological conditions. Currently, O3-based therapies rely on the low-dose concept i.e., the administration of low O3 concentrations able to induce a mild oxidative stress stimulating antioxidant and anti-inflammatory response without causing cell damage. In addition, low O3 concentrations are thought to activate cellular and molecular mechanisms responsible for analgesic and regenerative effects. Due to these properties, in the last decade interest has arisen in the fields of orthopedics and regenerative medicine on the potential of O3 to counteract joint diseases involving cartilage degeneration. In this pilot study, we have explored the anti-degenerative potential of O3 on knee articular cartilage explanted from a healthy adult rabbit and maintained in vitro. Light and transmission electron microscopy were used to monitor chondrocyte and extracellular matrix features of cartilage samples undergoing O3 treatment every three days for two weeks. Results demonstrated that low O3 concentrations act on chondrocytes and the molecular components of the extracellular matrix of articular cartilage explants, significantly improving their preservation under in vitro conditions, likely by promoting both protective and pro-regenerative pathways. This opens promising perspectives for further investigations on the therapeutic potential of O3 for the treatment of cartilage degeneration not only as painkilling and anti-inflammatory agent but also as a cartilage regenerative agent.
The hematopoietic stem cells supportive megakaryocytes as shapers of the bone marrow niche.
Arciprete F, Velardi V, Verachi P … +6 more , Carta C, Di Virgilio A, Roberti V, Vivacqua G, Rana R, Zingariello M
Eur J Histochem · 2025 Sep · PMID 41400273 · Full text
The bone marrow (BM) niche plays a pivotal role in regulating the fate of hematopoietic stem cells (HSCs), and its integrity changes significantly during aging and in rare hematological disease, as in myelofibrosis (MF)....
The bone marrow (BM) niche plays a pivotal role in regulating the fate of hematopoietic stem cells (HSCs), and its integrity changes significantly during aging and in rare hematological disease, as in myelofibrosis (MF). In this study, we investigated how the localization and dynamics of HSCs are influenced under physiological and pathological conditions by a newly identified by HSC-supportive megakaryocytes (MKs) subpopulation. Using huCD34tTA/TetO-H2BGFP reporter mice, we analyzed HSCs distribution within the BM and quantified nuclear green fluorescent protein (GFP) intensity to assess the repopulating potential of aged controls and mutated Gata1low mice for MF. In the control group of aged mice, cells with high levels of GFP are clustered, and adjacent to cells morphologically identifiable as supportive MKs. These clusters displayed homogeneous GFP intensity, indicating that HSCs with similar functional properties tend to co-localize in proximity to supportive MKs. By contrast, in aged huCD34/TET/Gata1low mice, GFP cells were predominantly isolated and showed reduced fluorescence intensity. Although the frequency of MKs with a supportive phenotype was increased in MF mice, analyses of GFP revealed that the ability of these MKs to maintain the HSCs in their niche was significantly impaired. Our results provide new insights on the maladaptive remodeling of the BM niche. They highlight the supportive role of MKs as potential key regulators of HSCs homeostasis. Despite their numerical expansion in MF, these cells are functionally compromised, thereby contributing to altered HSCs localization, mobilization, and to hematopoietic failure.
Genetic deletion of P-selectin prevents fibrosis development by inhibiting the neutrophil megakaryocyte emperipolesis in the Gata1 mouse model for myelofibrosis.
Arciprete F, Velardi V, Di Virgilio A … +7 more , Verachi P, Carta C, Pozzi G, Roberti V, Vivacqua G, Rana R, Zingariello M
Eur J Histochem · 2025 Sep · PMID 41400266 · Full text
Myelofibrosis (MF) is a rare chronic hematological disorder, within the family of myeloproliferative neoplasms. The MF patients present clinical abnormalities such as anemia, and thrombosis, as well as alterations in the...
Myelofibrosis (MF) is a rare chronic hematological disorder, within the family of myeloproliferative neoplasms. The MF patients present clinical abnormalities such as anemia, and thrombosis, as well as alterations in the bone marrow (BM) microenvironment, an increased number of megakaryocytes (MKs), most of which are found in emperipolesis with neutrophils. In MF, the MKs emperipolesis is induced by an altered MK secretome, containing increased levels of pro-inflammatory cytokines, proteins, and growth factors such as interleukin-8 (IL-8) and P-selectin (P-sel). These, allow the altered cell-to-cell interactions and cause the transforming growth factor-β (TGF-β) to be released into the BM microenvironment. This fibrogenic cytokine contributes to BM fibrosis and disease progression. Emperipolesis has already been identified as a pathobiological event that contributes to MF and it is widely recognized in the most advanced stages of the disease. In this study, we evaluated the role of P-sel in BM alterations associated with emperipolesis in the Gata1low mouse model of MF. Our data show that emperipolesis is driven by P-sel. Genetic ablation of P-sel rescued the BM microenvironment, by decreasing fibrosis, suggesting that pharmacological targeting of P-sel could contribute to reduce the BM dysfunction and disease progression.
Transient receptor potential canonical 3/5 attenuate endothelial damage-induced neointima formation without affecting endothelial cell proliferation.
Zeng W, Liu B, Yang L … +1 more , Guo R
Eur J Histochem · 2025 Sep · PMID 41258723 · Full text
Store-operated calcium channels (SOCCs) are involved in the process of cell proliferation; however, their expression levels differ among cell types and information on their effects in different cells is lacking. This stu...
Store-operated calcium channels (SOCCs) are involved in the process of cell proliferation; however, their expression levels differ among cell types and information on their effects in different cells is lacking. This study aimed to compare the differing effects of SOCCs on the proliferation of vascular smooth muscle cells (VSMCs) and vascular endothelial cells (VECs), and the repair ability of SOCC after vascular endothelial injury. Rat primary coronary VSMCs and VECs were cultured in vitro and expression levels of SOCC molecules were detected by western blotting and quantitative polymerase chain reaction. Various molecules were selected and transfected into VSMCs and VECs using an adenovirus vector, and cell proliferation, the cell cycle, and intracellular Ca2+ were then detected. We also established a rat carotid artery endothelial injury model to verify the results of the in vitro experiments. Expression levels of transient receptor potential canonical (TRPC) 3 and TRPC5 were higher in VSMCs than in VECs. Silencing TRPC3/5 significantly inhibited cell proliferation and Ca2+ influx in VSMCs, but not in VECs. Silencing TRPC3/5 after rat carotid artery endothelial injury inhibited neointima formation, with a better reparative effect on the endothelial cell layer than rapamycin. TRPC3/5 participates in the proliferation of VSMCs via SOCCs, and silencing its expression inhibits the formation of neointima after endothelial injury. However, this effect was not significant in VECs, suggesting that other compensatory pathways may have emerged.
Placental mesenchymal stem cell exosomes drive macrophage M2 polarization the miR-146a-5p/TRAF6 axis to ameliorate preeclampsia.
Liu X, Li R, Sun J … +2 more , Yang Y, Hu L
Eur J Histochem · 2025 Sep · PMID 41247022 · Full text
The functional state of placental mesenchymal stem cells (PMSCs) plays a critical role in maintaining maternal-fetal interface homeostasis during the pathogenesis of preeclampsia (PE). Given the limitations associated wi...
The functional state of placental mesenchymal stem cells (PMSCs) plays a critical role in maintaining maternal-fetal interface homeostasis during the pathogenesis of preeclampsia (PE). Given the limitations associated with direct stem cell transplantation, this study aimed to investigate the therapeutic potential of PMSC-derived exosomes and their carried miR-146a-5p. Clinical sample analysis revealed a significant downregulation of miR-146a-5p in placental tissues from PE patients, accompanied by impaired proliferation, migration, and angiogenic dysfunction of PMSCs. In an in vitro model, exosome intervention effectively reversed hypoxia-induced trophoblast cell apoptosis and enhanced migratory capacity. Furthermore, it promoted macrophage polarization towards the anti-inflammatory M2 phenotype and markedly improved the inflammatory cytokine secretion profile. In a PE mouse model, exosome treatment reduced maternal blood pressure and proteinuria levels, alleviated fetal growth restriction, and up-regulated the expression of M2 macrophage markers in placental tissue. Mechanistically, miR-146a-5p targeted TRAF6 to suppress NF-κB pathway activation, an effect that could be reversed by specific inhibitors. This study is the first to demonstrate that PMSC-derived exosomes, via the miR-146a-5p/TRAF6 axis, concurrently ameliorate trophoblast dysfunction and correct macrophage polarization imbalance. The efficient intercellular delivery of miR-146a-5p by exosomes underscores their potential as a novel targeted therapeutic strategy for PE.
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