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Background: Rhinoviruses (RV) are the major cause of common colds in healthy individuals and are associated with acute exacerbations in patients with chronic lung diseases. Yet, no vaccines or effective treatment against RV are available. This study investigated the effect of Euphorbium compositum SN (ECSN6), a multicomponent, multitarget medication made from natural ingredients, on the mucosal barrier network during RV infection. Methods: Mucociliary-differentiated airway epithelial cell cultures were infected with RV or sham, and treated with 20% ECSN6 or placebo twice daily. Barrier integrity was assessed by measuring transepithelial resistance (TER), permeability to inulin, and expression and localization of intercellular junctions proteins (IJ). Ciliary beat frequency (CBF), expression of pro-inflammatory cytokines, antiviral interferons and mucins, and viral load were also measured. C57BL/6 mice were infected intranasally with RV or sham and treated with 40% ECSN6 or placebo twice daily. Inflammation of sinunasal mucosa, localization of E-cadherin, viral load and mucin gene expression were determined. Results: ECSN6-treated, uninfected cell cultures showed small, but significant increase in TER over placebo, which was associated with enhanced localization of E-cadherin and ZO-1 to IJ. In RV-infected cultures, treatment with ECSN6, but not placebo prevented RV-induced (1) reduction in TER, (2) dissociation of E-cadherin and ZO-1 from the IJ, (3) mucin expression, and (4) CBF attenuation. ECSN6 also decreased RV-stimulated expression of pro-inflammatory cytokines and permeability to inulin. Although ECSN6 significantly increased the expression of some antiviral type I and type III interferons, it did not alter viral load. In vivo, ECSN6 reduced RV-A1-induced moderate inflammation of nasal mucosa, beneficially affected RV-A1-induced cytokine responses and Muc5ac mRNA expression and prevented RV-caused dissociation of E-cadherin from the IJ of nasal mucosa without an effect on viral clearance. Conclusions: ECSN6 prevents RV-induced airway mucosal barrier dysfunction and improves the immunological and mucociliary barrier function. ECSN6 may maintain integrity of barrier function by promoting localization of tight and adherence junction proteins to the IJ. This in turn may lead to the observed decrease in RV-induced pro-inflammatory responses in vitro. By improving the innate defenses of the airway mucosal barrier network, ECSN6 may alleviate respiratory symptoms caused by RV infections. [ABSTRACT FROM AUTHOR]

The presence of E‐cadherin⋯E‐cadherin interactions in the intercellular space (paracellular pathway) poses a notable limitation in drug delivery across the blood‐brain barrier (BBB). ADTC5 peptide has shown promising results in improving drug delivery across the BBB by modulating E‐cadherin⋯E‐cadherin interactions. However, the study of E‐cadherin⋯ADTC5 amino acid interactions using quantum mechanics approach has not been observed clearly. Herein, we observed the interaction between E‐cadherin⋯ADTC5 amino acids using density functional theory (DFT). Natural bond orbital (NBO), quantum theory of atoms in molecules (QTAIM), and reduced density gradient (RDG) analysis are performed to study the non‐covalent interaction in detail. The Arg55⋯Asp2 shows the strongest interaction between E‐cadherin⋯ADTC5 modulation, indicated by the highest stabilization energy (E(2)), and hydrogen bonding energy (EHB) about 22.04 and −6.90 kcal/mol, respectively. This interaction is dominated by hydrogen bonding. Such advancements could lead to significant improvements in therapeutic strategies for neurodegenerative diseases, where effective drug delivery across the BBB remains a major challenge. [ABSTRACT FROM AUTHOR]

Objective: Down-regulation of bronchial epithelial E-cadherin is an important of feature of severe asthma, including steroid-insensitive asthma. Yet, the mechanisms involved in E-cadherin disruption are not fully understood. This study was aimed to investigate the role of glucose transporter 1 (GLUT1) in dysregulation of E-cadherin in toluene diisocyanate (TDI)-induced steroid-insensitive asthma. Methods: A murine model of steroid-insensitive asthma was established by TDI sensitization and aerosol inhalation. Selective GLUT1 antagonists WZB117 and BAY876 were given to BALB/c mice after airway challenge. In vitro, primary human bronchial epithelial cells (HBECs) cultured in an airway-liquid interface (ALI) were exposed to TDI. Results: TDI exposure markedly up-regulated GLUT1 in murine lungs and HBECs. Pharmacological inhibition of GLUT1 with BAY876 decreased airway hyperresponsiveness, neutrophil and eosinophil accumulation, as well as type 2 inflammation in vivo. Besides, the TDI-induced down-regulated expression of full-length E-cadherin was also partly recovered, accompanied by inhibited secretion of soluble E-cadherin (sE-cadherin). WZB117 also exhibited mild therapeutic effects, though not significant. In vitro, treatment with GLUT1 inhibitor relieved the TDI-induced disruption of E-cadherin in HBECs. Conclusions: Taken together, our data demonstrated that GLUT1 modulates bronchial epithelial E-cadherin dysfunction production in TDI-induced steroid-insensitive asthma. [ABSTRACT FROM AUTHOR]

Objective: Actinic cheilitis (AC) is a chronic lesion that usually precedes the onset of squamous cell carcinoma of the lip. Microscopically, AC may exhibit epithelial dysplasia (ED). Twist is a transcription factor that regulates the mesenchymal phenotype through negative E‐cadherin regulation. This study evaluated Twist and E‐cadherin immunoexpression in AC with different ED degrees. Materials and Methods: Twist and E‐cadherin immunoexpression was evaluated semiquantitatively in the epithelium of 86 cases of AC with different ED degrees. Data obtained were submitted to the Mann–Whitney test and Spearman's correlation test. Results: Immunohistochemical analysis revealed nuclear and cytoplasmic Twist immunoreactivity in all epithelial layers except the cornified layer. In contrast, the membrane and cytoplasmic E‐cadherin immunoreactivity was observed in all epithelial layers except the cornified layer. No significance was observed between the scores of these proteins and the ED degree. It was observed a correlation between total Twist and total (p = 0.030) and membrane (p = 0.014) E‐cadherin and between nuclear Twist and cytoplasmic E‐cadherin (p = 0.030). Conclusions: The results suggest that the high immunoexpression of Twist is an early lip carcinogenesis event. However, it appears not to influence the progression of ED in AC. [ABSTRACT FROM AUTHOR]

Background/Objectives: Bladder cancer, predominantly urothelial carcinoma, is an important malignancy of the urinary system. Despite the same histologic grade and stage, some patients seem to have a worse prognosis. In this context, the epithelial–mesenchymal transition (EMT), characterized by the loss of E-cadherin and gain of vimentin expression, is an important process in tumor progression. Galectin-3, a lactose-binding protein involved in various cellular processes, has been associated with increased tumor cell migration, invasion, and treatment resistance. Methods: In this study, 223 bladder cancer cases were examined, and E-cadherin, vimentin, and galectin-3 expression was evaluated by immunohistochemical staining in tumor budding areas and invasive components. These markers were also correlated with clinicopathological parameters, including tumor grade and stage. Results: The results indicated a significant decrease in E-cadherin expression and an increase in vimentin staining in higher-grade and higher-stage tumors, supporting EMT involvement. Galectin-3 expression was notably higher in T1 high-grade tumors but decreased in T2 stage tumors. Despite this, no significant correlation was found between galectin-3 and E-cadherin or vimentin, suggesting a complex role of galectin-3 in EMT. Conclusions: High galectin-3 expression in T1 high-grade tumors highlights its potential role in early tumor progression and as a therapeutic target. However, the decrease in its expression in advanced stages underscores the need for further research to understand its multifaceted involvement in bladder cancer. These findings suggest that while galectin-3 may contribute to the EMT and early tumor progression, its exact role and potential as a therapeutic target require more detailed investigation. [ABSTRACT FROM AUTHOR]

The expression of markers associated with epithelial—mesenchymal transition (EMT) and extracellular matrix degradation in human uveal melanoma tissue samples and postequatorial zone of the choroid was assessed by immunohistochemical staining. Increased expression of EMT markers E-cadherin and vimentin was observed in the tumor. The ratio of MMP-9 to TIMP-1 proteins related to the extracellular matrix degradation was higher in the tumor. These results may indicate activation of EMT-like process in the uveal melanoma cells and degradation of the extracellular matrix, which can contribute to the development of collective invasion in uveal melanoma. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is known to have the worst outcome compared to the other forms of breast cancer. Moreover, molecular markers identified basal-like breast cancer (BLBC) phenotypes to be also related to a worse prognosis. In this study, we evaluated by immunohistochemistry (IHC) the prognostic significance of combining Cytokeratin-19 (CK19), E-cadherin, and Ki-67 tissue expression in triple-negative breast cancer (TNBC) cases presenting a basal-like (BLBC) or a non-basal-like (n-BLBC) phenotype to improve the selection and the monitoring of BC patients with a more aggressive outcome. Herein, when compared to n-BLBC, patients with BLBC showed a positive correlation with lymph node metastasis occurrence and lower survival rates. Immunohistochemistry analysis revealed significantly lower E-cadherin prevalence and higher prevalence of both CK19 and Ki-67 in BLBC when compared to n-BLBC. Spearman correlation showed that E-cadherin is negatively and significantly correlated to CK19 and Ki-67 expressions. Moreover, in BLBC, expressing both CK19 and Ki-67 combined with E-cadherin loss was associated with the worst relapse-free and overall survival. In conclusion, TNBC/BLBC phenotypes simultaneously losing E-cadherin and overexpressing CK19 and Ki-67 markers are the most aggressive forms. This combined analysis could be a predictive marker of poor prognosis. [ABSTRACT FROM AUTHOR]

Cell membrane-derived liposomes, termed Memposomes, serve as promising carriers for drug delivery due to their ability to closely mimic cells and efficiently target specific cells. Liposomes derived from cancer cell membranes, in particular, exhibit homologous targeting capabilities, making them potential candidates for cancer-specific drug delivery. However, the underlying mechanisms and specific proteins responsible for this homologous targeting phenomenon remain debated. This study focuses on the role of E-cadherin, a cell adhesion molecule implicated in homophilic adhesion, in influencing the homologous targeting ability of Memposomes derived from cancer cell membranes. E-cadherin expression patterns were assessed in various cell lines, categorizing them into E-cadherin-positive and -negative groups. Memposomes were produced for each group, and their targeting tendencies were evaluated. This study confirmed that E-cadherin expression significantly influenced the homologous targeting ability of the Memposomes. The cell lines with higher E-cadherin expression levels exhibited a more pronounced homologous targeting effect. This research demonstrates that cell adhesion molecules, particularly E-cadherin involved in homophilic adhesion, play a pivotal role in influencing the cell targeting ability of Memposomes. This study further validates the stability, safety, and purity of Memposomes, emphasizing their potential as effective drug delivery vehicles for the development of cell-specific therapies. [ABSTRACT FROM AUTHOR]

SGEF (also known as ARHGEF26), a RhoG specific GEF, can form a ternary complex with the Scribble polarity complex proteins Scribble and Dlg1, which regulates the formation and maintenance of adherens junctions and barrier function of epithelial cells. Notably, silencing SGEF results in a dramatic downregulation of both E-cadherin and ZO-1 (also known as TJP1) protein levels. However, the molecular mechanisms involved in the regulation of this pathway are not known. Here, we describe a novel signaling pathway governed by the Scribble–SGEF–Dlg1 complex. Our results show that the three members of the ternary complex are required to maintain the stability of the apical junctions, ZO-1 protein levels and tight junction (TJ) permeability. In contrast, only SGEF is necessary to regulate E-cadherin levels. The absence of SGEF destabilizes the E-cadherin–catenin complex at the membrane, triggering a positive feedback loop that exacerbates the phenotype through the repression of E-cadherin transcription in a process that involves the internalization of E-cadherin by endocytosis, β-catenin signaling and the transcriptional repressor Slug (also known as SNAI2). [ABSTRACT FROM AUTHOR]

Pharyngeal endoderm cells undergo convergence and extension (C&E), which is essential for endoderm pouch formation and craniofacial development. Our previous work implicates Gα13/RhoAmediated signaling in regulating this process, but the underlying mechanisms remain unclear. Here, we have used endoderm-specific transgenic and Gα13mutant zebrafish to demonstrate that Gα13 plays a crucial role in pharyngeal endodermC&E by regulating RhoA activation and E-cadherin expression. We showed that during C&E, endodermal cells gradually establish stable cell-cell contacts, acquire apical-basal polarity and undergo actomyosin-driven apical constriction, which are processes that require Gα13. Additionally, we found that Gα13-deficient embryos exhibit reduced E-cadherin expression, partially contributing to endoderm C&E defects. Notably, interfering with RhoA function disrupts spatial actomyosin activation without affecting E-cadherin expression. Collectively, our findings identify crucial cellular processes for pharyngeal endoderm C&E and reveal that Gα13 controls this through two independent pathways - modulating RhoA activation and regulating E-cadherin expression - thus unveiling intricate mechanisms governing pharyngeal endoderm morphogenesis. [ABSTRACT FROM AUTHOR]

Objective: To investigate the accuracy of gingival crevicular fluid (GCF) E‐cadherin and total antioxidant capacity (TAC) to discriminate periodontal health from disease. Subjects and Methods: GCF samples were collected from participants with periodontal health (control), gingivitis, and periodontitis (n = 25 each group). The latter group was further subdivided according to stage (S) and grade. Periodontal parameters were recorded then levels of biomarkers were assayed using ELISA and antioxidant status by use of the Total Antioxidant Capacity Assay for E‐cadherin and TAC, respectively. Results: All periodontal parameters were significantly higher in periodontally diseased groups than controls. The GCF E‐cadherin significantly increased in gingivitis and periodontitis (S2 to S4) cases as compared to controls. Level of this protein in GCF samples from periodontitis S3 was significantly higher than in gingivitis and S2 groups. The GCF‐TAC level was significantly higher in controls than in periodontally diseased groups. No significant differences were observed in the levels of these proteins between grade B and C periodontitis. Both molecules could discriminate periodontal health from gingivitis and periodontitis stages and differentiating periodontitis S3 from gingivitis and other periodontitis stages. Conclusions: Levels of TAC and unbounded E‐cadherin in GCF samples exhibited promising diagnostic abilities to differentiate periodontal health and disease. [ABSTRACT FROM AUTHOR]

Di-(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer that has adverse health effects. Most phthalates exhibit reproductive toxicity and are associated with diseases such as cardiovascular disorders. However, the effect of DEHP exposure on acute hypoxia/reperfusion injury remains unknown. Therefore, we assessed whether hypoxia/reperfusion injury is aggravated by exposure to DEHP and investigated plausible underlying mechanisms, including oxidative stress and expression of cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) and endothelial junctional proteins. bEnd.3 cells were exposed to DEHP and subsequently subjected to oxygen–glucose deprivation (OGD). Cell viability was analyzed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) proliferation assay. The effect of DEHP/OGD/reoxygenation (R) was evaluated by assessing the levels of NO, reactive oxygen species (ROS), and PGE2. The expression of COX-2, cleaved caspase-3, cleaved PARP, inducible nitric oxide synthase (iNOS), and the endothelial tight junction proteins claudin-5 and ZO-1 was evaluated using quantitative polymerase chain reaction and western blotting. OGD/R decreased cell viability, and DEHP exposure before OGD/R further aggravated cell viability. DEHP/OGD/R significantly increased NO, PGE2, and ROS production following OGD/R. In the DEHP/OGD/R group, iNOS, COX-2, cleaved caspase-3, and cleaved PARP expression increased, and claudin-5 and ZO-1 levels decreased compared with those in the OGD/R group. E-Cadherin expression decreased significantly after DEHP/OGD/R exposure compared with that after OGD/R; this decrease in expression was recovered by treatment with the COX-2 inhibitor indomethacin and antioxidant N-acetylcysteine. Exposure to DEHP exacerbated hypoxia-reoxygenation injury. The enhanced damage upon DEHP exposure was associated with increased oxidative stress and COX-2 expression, leading to E-cadherin downregulation and increased apoptosis. [ABSTRACT FROM AUTHOR]

Alpha T-catenin has recently been identified as a crucial tumor suppressor in various cancer types, with roles that go beyond just providing structural support in adherens junctions. This review brings together recent findings on alpha T-catenin's important involvement in key signaling pathways related to cancer progression. We present strong evidence of its regulatory role in Wnt signaling, a pathway often disrupted in colorectal cancer, and explain how it inhibits cell proliferation and tumor growth. We also discuss the significant downregulation of alpha T-catenin in colorectal cancers and its potential as a prognostic marker. Moreover, this review looks at how increasing alpha T-catenin levels can reduce tumor growth and spread, suggesting new therapeutic strategies. Additionally, we reveal alpha T-catenin's unexpected impact on NF-κB signaling in basal E-cadherin-negative breast cancer, expanding its importance across different cancer types. By bringing these findings together, we provide a thorough understanding of alpha T-catenin's tumor-suppressing actions, setting the stage for new targeted therapies and diagnostic tools in cancer treatment. [ABSTRACT FROM AUTHOR]

Morphine has been suggested to affect cancer cell dynamics and decrease survival rates in lung cancer patients at specific doses, but the precise mechanisms poorly understood. In this study, we aimed to investigate the molecular mechanisms by which morphine modulates the malignant characteristics of non-small cell lung cancer. Cell proliferation was assessed via the Cell Counting Kit-8 assay, and cell migration and invasion were examined via wound healing and Transwell assays. We employed immunofluorescence staining to evaluate E-cadherin expression in A549 and Lewis lung cancer (LLC) cell lines and immunohistochemistry to evaluate E-cadherin expression in nude mice tumours. Additionally, the in vivo effects of morphine on lung cancer progression were explored in a xenograft tumour experiments, in which naloxone was used as a morphine antagonist. Western blot analysis was performed to detect E-cadherin, phosphorylated mTOR (p-mTOR), mTOR, phosphorylated AKT (p-AKT), AKT, phosphorylated PI3K (p-PI3K), and PI3K protein levels in A549 and LLC cells as well as in tumour samples. Morphine (10 µM) significantly increased the proliferation of A549 and LLC cells in vitro (p < 0.05). It also enhanced the migratory and invasive capacities of these cell lines (p < 0.01). Mechanistically, morphine treatment (10 µM) led to a reduction in the expression of E-cadherin, and an increase in the phosphorylation of PI3K, AKT, and mTOR in A549 and LLC cells (p < 0.01). Morphine treatment (1.5 mg/kg) also reduced E-cadherin expression in xenograft tumours and promoted tumour growth in vivo (p < 0.05). This effect was reversed by naloxone (0.1 mg/kg). The results demonstrated that morphine stimulates the malignant proliferation of A549 and LLC cell lines and promotes xenograft tumour growth. Perhaps by specifically targeting MOR, morphine triggers a signalling cascade that activates the PI3K/AKT/mTOR pathway while inhibiting the EMT marker E-cadherin, which may consequently promote the progression of lung cancer. [ABSTRACT FROM AUTHOR]

For centuries, the meninges have been described as three membranes: the inner pia, middle arachnoid and outer dura. It was therefore sensational when in early 2023 Science magazine published a report of a previously unrecognized — 4th — meningeal membrane located between the pia and arachnoid. Multiple features were claimed for this new membrane: a single cell layer marked by the transcription factor Prox1 that formed a barrier to low molecular weight substances and separated the subarachnoid space (SAS) into two fluid-filled compartments, not one as previously described. These features were further claimed to facilitate unidirectional glymphatic cerebrospinal fluid transport. These claims were immediately questioned by several researchers as misinterpretations of the authors' own data. The critics argued that (i) the 4th meningeal membrane as claimed did not exist as a separate structure but was part of the arachnoid, (ii) the "outer SAS" compartment was likely an artifactual subdural space created by the experimental procedures, and (iii) the 4th membrane barrier property was confused with the arachnoid barrier. Subsequent publications in late 2023 indeed showed that Prox1 + cells are embedded within the arachnoid and located immediately inside of and firmly attached to the arachnoid barrier cells by adherens junctions and gap junctions. In a follow-up study, published in this journal, the lead authors of the Science paper Kjeld Møllgård and Maiken Nedergaard reported additional observations they claim support the existence of a 4th meningeal membrane and the compartmentalization of the SAS into two non-communicating spaces. Their minor modification to the original paper was the 4th meningeal membrane was better observable at the ventral side of the brain than at the dorsal side where it was originally reported. The authors also claimed support for the existence of a 4th meningeal membrane in classical literature. Here, we outline multiple concerns over the new data and interpretation and argue against the claim there is prior support in the literature for a 4th meningeal membrane. [ABSTRACT FROM AUTHOR]

Transmembrane protein 52B (TMEM52B), a newly identified tumor‐related gene, has been reported to regulate various tumors, yet its role in nasopharyngeal carcinoma (NPC) remains unclear. Transcriptomic analysis of NPC cell lines reveals frequent overexpression of TMEM52B, and immunohistochemical results show that TMEM52B is associated with advanced tumor stage, recurrence, and decreased survival time. Depleting TMEM52B inhibits the proliferation, migration, invasion, and oncogenesis of NPC cells in vivo. TMEM52B encodes two isoforms, TMEM52B‐P18 and TMEM52B‐P20, differing in their N‐terminals. While both isoforms exhibit similar pro‐oncogenic roles and contribute to drug resistance in NPC, TMEM52B‐P20 differentially promotes metastasis. This functional discrepancy may be attributed to their distinct subcellular localization; TMEM52B‐P18 is confined to the cytoplasm, while TMEM52B‐P20 is found both at the cell membrane and in the cytoplasm. Mechanistically, cytoplasmic TMEM52B enhances AKT phosphorylation by interacting with phosphoglycerate kinase 1 (PGK1), fostering NPC growth and metastasis. Meanwhile, membrane‐localized TMEM52B‐P20 promotes E‐cadherin ubiquitination and degradation by facilitating its interaction with the E3 ubiquitin ligase NEDD4, further driving NPC metastasis. In conclusion, the TMEM52B‐P18 and TMEM52B‐P20 isoforms promote the metastasis of NPC cells through different mechanisms. Drugs targeting these TMEM52B isoforms may offer therapeutic benefits to cancer patients with varying degrees of metastasis. [ABSTRACT FROM AUTHOR]

Glucose metabolism produces lactate and hydrogen ions in an anaerobic environment. Fetuses with intrauterine growth restriction are considered to become progressively lactacidemic as well as hypoxic. Roles of lactate in the placenta in the presence of fetal growth restriction (FGR) remain to be clarified. Immunohistochemical localization of lactate-related substances, such as a receptor for lactate (hydroxy-carboxylic acid 1 receptor (HCA1 receptor/GPR81)), monocarboxylate transporters (MCTs) for lactate, lactate dehydrogenases (LDHs), and proteins expressed in syncytiotrophoblasts or cytotrophoblasts was examined in placentas of appropriate weight for gestational age (AGA) fetus and those showing FGR. Immunoreactivity for the HCA1 receptor was present in the cytoplasm of some trophoblasts, predominantly localized to their basal (fetus-facing) side, and was frequently colocalized with that for E-cadherin or serine peptidase inhibitor, Kunitz type 1 (SPINT1), a marker protein of cytotrophoblasts. Immunoreactivity for MCT1 and MCT4 was present on the basal and the microvillous (maternal-facing) membranes of trophoblasts in both groups, respectively. Clear immunoreactivity for LDHA and LDHB was also observed in the cytoplasm of trophoblasts, mainly localized to their basal side. However, there were no significant differences in immunohistochemically stained areas of lactate-related substances between AGA and late-onset FGR groups. On the other hand, there were correlations between coefficients of the presence of chorioamnionitis and the values of LDHB and E-cadherin. Immunohistochemical localization of the HCA1 receptor was predominantly observed in the cytoplasm located on the basal side of trophoblasts, suggesting a role of lactate in human placental development, including syncytialization. • Immunoreactivity for the HCA1 receptor is in the cytoplasm of cytotrophoblasts. • Immunoreactivity for MCT1 is in the basal membrane of trophoblasts. • Immunoreactivity for MCT4 is in the microvillous membrane of trophoblasts. • Localization of lactate receptor/transporters are comparable between AGA and FGR. [ABSTRACT FROM AUTHOR]

Background: Endometriosis and uterine fibroids are benign conditions frequently linked to subfertility/infertility. Recent research has highlighted the importance of epithelial–mesenchymal transition between embryonic and endometrial cells in the context of embryo implantation. Additionally, the adverse endometrial environment during implantation has been proposed as a mechanism contributing to infertility in endometriosis. Nevertheless, the role of cadherin molecule alterations in relation to endometrial receptivity and embryo invasion remains a subject of controversy. Methods: We investigated the expression patterns of E-cadherin and N-cadherin in the endometria of women with ovarian endometrioma or uterine fibroids and assessed whether they differed from those of healthy women. We enrolled 17 women with ovarian endometrioma, 16 with uterine fibroids, and 6 healthy women. Endometrial tissues were obtained at the mid-secretory phase on days 19–24 of the menstrual cycle. The E-cadherin and N-cadherin mRNA and protein expression levels were measured using quantitative reverse transcriptase polymerase chain reaction and Western blot analysis, respectively. Results: The E-cadherin and N-cadherin mRNA expression levels were higher and lower, respectively, in the endometrium of women with ovarian endometrioma than in those of the controls. In the endometrium of women with uterine fibroids, similar patterns with higher E-cadherin and lower N-cadherin levels were observed compared with that of the controls. Protein expression showed similar patterns. Conclusions: Our findings revealed higher E-cadherin expression and lower N-cadherin expression in the endometria of women with infertility-related diseases than in those of healthy women in the mid-secretory phase. This suggests a resistance to endometrial receptivity, potentially reflecting mesenchymal–epithelial transition properties. [ABSTRACT FROM AUTHOR]

Objectives: Renal cell carcinoma (RCC) is the most common cancer of the kidney. This study aims to evaluate the potential predictive value of E-cadherin, a marker of the epithelial mesenchymal transit (EMT) process that has been associated with tumor metastasis. Methods: We searched PubMed, Embase, and Cochrane Library to identify prospective studies. Hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs) were summarized to validate the relationship between E-cadherin and survival and clinical characteristics. The quality of the included studies was assessed using the NOS table. Then, we analyzed genetic data and clinical characteristics from The Cancer Genome Atlas Program (TCGA) database using R language with the dplyr package for validation. Results: Including 21 articles. The analysis revealed a strong link between high E-cadherin expression and favorable prognosis (for OS, HR = 0.35, 95% CI: 0.19–0.62; for PFS, HR = 0.19, 95% CI: 0.03–0.53; for DSS, HR = 0.25, 95% CI: 0.08–0.76; for RFS, HR = 0.71, 95% CI: 0.44–1.16; for DFS, HR = 0.28, 95% CI: 0.13-0.61; for T stage, OR = 0.21, 95% CI: 0.11–0.41; for N stage, OR = 0.07, 95%CI: 0.02-0.25; for M stage, OR = 0.12, 95% CI: 0.02–0.60; for clinical stage, OR = 0.29, 95% CI: 0.18–0.47; for nuclear grade, OR = 0.23, 95% CI: 0.13–0.41; for tumor size, OR = 0.49, 95% CI: 0.26–0.92). The findings were supported by bioinformatic analysis which used TCGA RCC patient's cohort (P < 0.01). Conclusion: Based on the current data, E-cadherin may predict a better prognosis in RCC patients. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) poses a significant challenge because of the difficulty in identifying aggressive tumors, leading to overtreatment and missed personalized therapies. Although only 8% of cases progress beyond the prostate, the accurate prediction of aggressiveness remains crucial. Thus, this study focused on studying retinoblastoma phosphorylated at Serine 249 (Phospho-Rb S249), N-cadherin, β-catenin, and E-cadherin as biomarkers for identifying aggressive PCa using a logistic regression model and a classification and regression tree (CART). Using immunohistochemistry (IHC), we targeted the expression of these biomarkers in PCa tissues and correlated their expression with clinicopathological data of the tumor. The results showed a negative correlation between E-cadherin and β-catenin with aggressive tumor behavior, whereas Phospho-Rb S249 and N-cadherin positively correlated with increased tumor aggressiveness. Furthermore, patients were stratified based on Gleason scores and E-cadherin staining patterns to evaluate their capability for early identification of aggressive PCa. Our findings suggest that the classification tree is the most effective method for measuring the utility of these biomarkers in clinical practice, incorporating β-catenin, tumor grade, and Gleason grade as relevant determinants for identifying patients with Gleason scores ≥ 4 + 3. This study could potentially benefit patients with aggressive PCa by enabling early disease detection and closer monitoring. [ABSTRACT FROM AUTHOR]

Abstract Background Rhinoviruses (RV) are the major cause of common colds in healthy individuals and are associated with acute exacerbations in patients with chronic lung diseases. Yet, no vaccines or effective treatment against RV are available. This study investigated the effect of Euphorbium compositum SN (ECSN6), a multicomponent, multitarget medication made from natural ingredients, on the mucosal barrier network during RV infection. Methods Mucociliary-differentiated airway epithelial cell cultures were infected with RV or sham, and treated with 20% ECSN6 or placebo twice daily. Barrier integrity was assessed by measuring transepithelial resistance (TER), permeability to inulin, and expression and localization of intercellular junctions proteins (IJ). Ciliary beat frequency (CBF), expression of pro-inflammatory cytokines, antiviral interferons and mucins, and viral load were also measured. C57BL/6 mice were infected intranasally with RV or sham and treated with 40% ECSN6 or placebo twice daily. Inflammation of sinunasal mucosa, localization of E-cadherin, viral load and mucin gene expression were determined. Results ECSN6-treated, uninfected cell cultures showed small, but significant increase in TER over placebo, which was associated with enhanced localization of E-cadherin and ZO-1 to IJ. In RV-infected cultures, treatment with ECSN6, but not placebo prevented RV-induced (1) reduction in TER, (2) dissociation of E-cadherin and ZO-1 from the IJ, (3) mucin expression, and (4) CBF attenuation. ECSN6 also decreased RV-stimulated expression of pro-inflammatory cytokines and permeability to inulin. Although ECSN6 significantly increased the expression of some antiviral type I and type III interferons, it did not alter viral load. In vivo, ECSN6 reduced RV-A1-induced moderate inflammation of nasal mucosa, beneficially affected RV-A1-induced cytokine responses and Muc5ac mRNA expression and prevented RV-caused dissociation of E-cadherin from the IJ of nasal mucosa without an effect on viral clearance. Conclusions ECSN6 prevents RV-induced airway mucosal barrier dysfunction and improves the immunological and mucociliary barrier function. ECSN6 may maintain integrity of barrier function by promoting localization of tight and adherence junction proteins to the IJ. This in turn may lead to the observed decrease in RV-induced pro-inflammatory responses in vitro. By improving the innate defenses of the airway mucosal barrier network, ECSN6 may alleviate respiratory symptoms caused by RV infections.

Abstract Morphine has been suggested to affect cancer cell dynamics and decrease survival rates in lung cancer patients at specific doses, but the precise mechanisms poorly understood. In this study, we aimed to investigate the molecular mechanisms by which morphine modulates the malignant characteristics of non-small cell lung cancer. Cell proliferation was assessed via the Cell Counting Kit-8 assay, and cell migration and invasion were examined via wound healing and Transwell assays. We employed immunofluorescence staining to evaluate E-cadherin expression in A549 and Lewis lung cancer (LLC) cell lines and immunohistochemistry to evaluate E-cadherin expression in nude mice tumours. Additionally, the in vivo effects of morphine on lung cancer progression were explored in a xenograft tumour experiments, in which naloxone was used as a morphine antagonist. Western blot analysis was performed to detect E-cadherin, phosphorylated mTOR (p-mTOR), mTOR, phosphorylated AKT (p-AKT), AKT, phosphorylated PI3K (p-PI3K), and PI3K protein levels in A549 and LLC cells as well as in tumour samples. Morphine (10 µM) significantly increased the proliferation of A549 and LLC cells in vitro (p

Streptococcus pneumoniae, a common cause of community-acquired bacterial pneumonia, can cross the respiratory epithelial barrier to cause lethal septicemia and meningitis. S. pneumoniae pore-forming toxin pneumolysin (PLY) triggers robust neutrophil (PMN) infiltration that promotes bacterial transepithelial migration in vitro and disseminated disease in mice. Apical infection of polarized respiratory epithelial monolayers by S. pneumoniae at a multiplicity of infection (MOI) of 20 resulted in recruitment of PMNs, loss of 50% of the monolayer, and PMN-dependent bacterial translocation. Reducing the MOI to 2 decreased PMN recruitment two-fold and preserved the monolayer, but apical-to-basolateral translocation of S. pneumoniae remained relatively efficient. At both MOI of 2 and 20, PLY was required for maximal PMN recruitment and bacterial translocation. Co-infection by wild-type S. pneumoniae restored translocation by a PLY-deficient mutant, indicating that PLY can act in trans. Investigating the contribution of S. pneumoniae infection on apical junction complexes in the absence of PMN transmigration, we found that S. pneumoniae infection triggered the cleavage and mislocalization of the adherens junction (AJ) protein E-cadherin. This disruption was PLY-dependent at MOI of 2 and was recapitulated by purified PLY, requiring its pore-forming activity. In contrast, at MOI of 20, E-cadherin disruption was independent of PLY, indicating that S. pneumoniae encodes multiple means to disrupt epithelial integrity. This disruption was insufficient to promote bacterial translocation in the absence of PMNs. Thus, S. pneumoniae triggers cleavage and mislocalization of E-cadherin through PLY-dependent and -independent mechanisms, but maximal bacterial translocation across epithelial monolayers requires PLY-dependent neutrophil transmigration.

The current study aims to evaluate the levels of miR-34a, RASSF1A, and E-cadherin in relation to the levels of isoform B of progesterone receptor (PRB) in endometrioid carcinoma (EC) and atypical hyperplasia (AEH) and their association with clinicopathological parameters. 105 cases (35 EC, 35 AEH, and 35 control) were involved in this study. Cases of AEH received treatment, and other samples were obtained after 6 months to assess the response. E-cadherin and PRB were assessed by immunohistochemistry (IHC), RASSFA methylation by MSP-PCR, and its serum level by ELISA and miR-34a via quantitative PCR. The expressions of miR-34a, RASSF1A, E-cadherin, and PRB differ among the studied groups; all were higher in normal compared with AEH and EC, with a statistically significant difference. The higher PRB expression and decreased miR-34a and RASSF1A expression were associated with resistance to hormonal therapy in AEH. High PRB in EC is associated with lower RASSFA1, E-cadherin, and miR-34a. Decreased expressions of RASSF1A, miR-34a, and E-cadherin had a significant connection to advanced stages. Expression of PRB and miR-34a and serum levels of RASSF1A predict response to treatment in cases of AEH. High PRB and low E-cadherin expression are associated with progressive disease in EC. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) poses a significant challenge because of the difficulty in identifying aggressive tumors, leading to overtreatment and missed personalized therapies. Although only 8% of cases progress beyond the prostate, the accurate prediction of aggressiveness remains crucial. Thus, this study focused on studying retinoblastoma phosphorylated at Serine 249 (Phospho-Rb S249), N-cadherin, β-catenin, and E-cadherin as biomarkers for identifying aggressive PCa using a logistic regression model and a classification and regression tree (CART). Using immunohistochemistry (IHC), we targeted the expression of these biomarkers in PCa tissues and correlated their expression with clinicopathological data of the tumor. The results showed a negative correlation between E-cadherin and β-catenin with aggressive tumor behavior, whereas Phospho-Rb S249 and N-cadherin positively correlated with increased tumor aggressiveness. Furthermore, patients were stratified based on Gleason scores and E-cadherin staining patterns to evaluate their capability for early identification of aggressive PCa. Our findings suggest that the classification tree is the most effective method for measuring the utility of these biomarkers in clinical practice, incorporating β-catenin, tumor grade, and Gleason grade as relevant determinants for identifying patients with Gleason scores ≥ 4 + 3. This study could potentially benefit patients with aggressive PCa by enabling early disease detection and closer monitoring.

Objective(s): Esophageal cancer stem cells (ECSCs) have been identified as the subset of cells within esophageal squamous cell carcinoma that possess tumorigenic, invasive, and metastatic properties. One important aspect of cancer metastasis is the binding of sialyl-Lewis X (CD15s) with E- or P-selectin, which facilitates the adhesion and migration of cancer cells to distant sites. This study was conducted to investigate the impact of fucosylation processes on the metastatic behavior of ECSCs.Materials and Methods: The esophageal cancer cell line (KYSE-30) was cultured and divided into control and 2F-peracetyl fucose (2F-PerAcFuc) treated groups. Spheres were harvested from these cultures. Cell invasion assay and qPCR were conducted to examine migration and marker expression in both groups. Cancer cell line-derived xenografts were established in nude mice to validate findings in vivo.Results: Our results initially indicated that the addition of 2F-PerAcFuc, an inhibitor of fucosylation, resulted in the down-regulation of the Fut3/CD15s pathway in both cancer stem-like cells and the xenograft model. Measurements of subcutaneous xenograft tumor volume revealed a significant decrease in tumor size among nude mice after treatment with 2F-PerAcFuc. Additionally, a reduction in Fut8/E-cadherin levels was observed in the xenograft model of nude mice. Furthermore, the administration of 2F-PerAcFuc lowered the levels of fucosylated glycoconjugates in nude mice.Conclusion: Our data suggest that inhibition of fucosyltransferase 3 and 8 can reduce the metastatic capacity of cancer stem-like cells by down-regulating CD15s and E-cadherin in a mouse model of esophageal cancer.

Background:E-cadherin is an adhesion molecule that is frequently expressed in normal epithelial tissues. It is essential for many cellular processes, including organ formation, stratification, and epithelial polarization. Objective:This study examines E-cadherin expression for subclassifying invasive breast cancer. E-cadherin expression also decreased with age, histopathological type, grade, and stage. Materials and Methods:This prospective study included 249 breast cancer patients who underwent surgery at a private facility in Baghdad, Iraq. The patients’ clinical data were analyzed, focusing on age, histopathological type, tumor grade, and tumor stage. Immunohistochemical and histopathological processing and staining were performed to evaluate E-cadherin status in the tumor cells. Results:Mean age of patients 47.92 ± 10.79 years, most age group 40–49 (35.7%), most histopathological type of breast cancer invasive ductal carcinoma (IDC; 81.1%), grade II (67.9%), and stage II (78.3%). Patients have +3 E-cadherin (79.5%). Grade III breast cancer patients have 98% +3 E-cadherin. E-cadherin is unrelated to age, histopathological type, or stage. Conclusion:Decreased E-cadherin expression in breast cancer is associated with higher tumor grade and estrogen receptor status. However, its significance as a prognostic or predictive marker is limited in IDC and special varieties. The study found no significant correlation between E-cadherin expression and age group, histopathological type, or breast cancer stage.

Borderline ovarian tumours (BOTs) show intriguing characteristics distinguishing them from other ovarian tumours. The aim of the systematic review was to analyse the spectrum of molecular changes found in BOTs and discuss their significance in the context of the overall therapeutic approach. The systematic review included articles published between 2000 and 2023 in the databases: PubMed, EMBASE, and Cochrane. After a detailed analysis of the available publications, we qualified for the systematic review: 28 publications on proto-oncogenes: BRAF, KRAS, NRAS, ERBB2, and PIK3CA, 20 publications on tumour suppressor genes: BRCA1/2, ARID1A, CHEK2, PTEN, 4 on adhesion molecules: CADM1, 8 on proteins: B-catenin, claudin-1, and 5 on glycoproteins: E-Cadherin. In addition, in the further part of the systematic review, we included eight publications on microsatellite instability and three describing loss of heterozygosity in BOT. Molecular changes found in BOTs can vary on a case-by-case basis, identifying carcinogenic mutations through molecular analysis and developing targeted therapies represent significant advancements in the diagnosis and treatment of ovarian malignancies. Molecular studies have contributed significantly to our understanding of BOT pathogenesis, but substantial research is still required to elucidate the relationship between ovarian neoplasms and extraneous disease, identify accurate prognostic indicators, and develop targeted therapeutic approaches.

Listeriosis is highly prevalent in the animal farming industry, with Listeria monocytogenes as the causative pathogen. To identify potential therapeutic targets for LM infection, we investigated the mechanisms of LM infection in goat uteri. We inoculated a group of goats with LM via jugular vein injection, isolated and raised them, and subsequently collected sterile samples of their uterine tissue after they exhibited clinical symptoms of LM infection. We used Giemsa staining, immunohistochemical staining, real-time qPCR, and Western blotting as experimental methods.First, we investigated the mechanism of Listeria monocytogenes (LM) infection in the goat uterus by examining the expression levels of listeriolysin O, E-cadherin, and tyrosine kinase c-Met in the uterus. Furthermore, we investigated the impact of LM infection on uterine autophagy and cell apoptosis. The results indicate that the injection of LM into the goats' jugular veins leads to LM infection in the goats' uteri. During LM survival inside the goat uterine cells, there is a significant increase in the expression levels of LLO, E-cadherin, and c-Met in the host uterine tissue. This suggests that LM may potentially infect goat uteri through the InlA/E-cadherin and InlB/c-Met pathways. Furthermore, LM infection increases the levels of apoptosis and autophagy in goat uteri. Apoptosis genes Bcl-2 and Bax, as well as autophagyrelated genes LC3B, PINK1, and Parkin, exhibit varying degrees of changes in localization and expression in goat uteri, mediating the occurrence of apoptotic and autophagic responses. [ABSTRACT FROM AUTHOR]

Invasive lobular carcinoma exhibits unique morphological features frequently associated with alterations in CDH1. Although some studies have identified abnormalities in adhesion factors other than E-cadherin, the molecular mechanisms underlying E-cadherin abnormalities in CDH1-unaltered invasive lobular carcinoma remain poorly understood. In this study, we investigated the molecular underpinnings of E-cadherin dysregulation in invasive lobular carcinoma in the absence of CDH1 gene alterations, using comprehensive bioinformatic analyses. We conducted a comparative study of CDH1-mutated and non-mutated invasive lobular carcinoma and evaluated the differences in mRNA levels, reverse-phase protein array, methylation, and miRNAs. We observed that invasive lobular carcinoma cases without CDH1 alterations exhibited a significantly higher incidence of the Claudin-low subtype (p < 0.01). The results of the reverse-phase protein array indicate no significant difference in E-cadherin expression between CDH1-mutated and non-mutated cases. Therefore, abnormalities in E-cadherin production also exist in CDH1 non-mutated invasive lobular carcinoma. Considering that there are no differences in mRNA levels and methylation status, post-translational modifications are the most plausible explanation for the same. Hence, future studies should focus on elucidating the mechanism underlying E-cadherin inactivation via post-translational modifications in CDH1 non-mutated invasive lobular carcinoma. [ABSTRACT FROM AUTHOR]

Background: Breast cancer recurrence and lymph node metastasis significantly impact patient outcomes. Understanding the molecular mechanisms behind these processes is crucial for developing effective treatments. CCN5 and E-cadherin are proteins involved in cell adhesion and epithelial-mesenchymal transition (EMT), playing roles in breast cancer progression. Objective: This study aimed to analyze the expression levels and clinical significance of CCN5 and E-cadherin in primary and recurrent breast cancer lesions. Methods: Immunohistochemical staining using the SP method was performed to detect CCN5 and E-cadherin expression levels in 28 normal breast tissue samples, 52 primary breast cancer lesions, and paired recurrent chest wall lesions. The expression levels of these proteins were compared across different tissue types and correlated with lymph node metastasis. Results: CCN5 and E-cadherin expression levels significantly differed among normal breast tissues, primary breast cancer lesions, and recurrent lesions (χ2 = 18.934 and χ2 = 14.516, p < 0.05). Primary breast cancer lesions exhibited higher CCN5 and E-cadherin expression levels compared with recurrent lesions and normal tissues, although these differences were not statistically significant. Patients without lymph node metastases exhibited significantly higher expression levels of CCN5 and E-cadherin compared with those with lymph node metastases (χ2 = 9.775, χ2 = 9.1479, p < 0.05). A positive correlation between CCN5 and E-cadherin expression levels was found in breast cancer tissues (r = 0.398, p < 0.001). Conclusion: CCN5 and E-cadherin were expressed at lower levels in recurrent breast cancer tissues and those with lymph node metastases, indicating their potential roles in breast cancer recurrence and metastasis. These findings suggest that CCN5 and E-cadherin might work synergistically to influence breast cancer progression. [ABSTRACT FROM AUTHOR]

Background/Objectives. Novel diagnostic and therapeutic approaches are needed to improve the clinical management of nonfunctioning pituitary neuroendocrine tumors (NF-PitNETs). Here, the expression of two proteins controlling the epithelial–mesenchymal transition (EMT)—an underlying NF-PitNET pathogenic mechanism—were analyzed as prognostic markers: E-cadherin (E-Cad) and KLHL14. Methods. The immunohistochemistry characterization of KLHL14 and E-Cad subcellular expression in surgical specimens of 12 NF-PitNET patients, with low and high invasiveness grades (respectively, Ki67+ < and ≥3%) was carried out. Results. The analysis of healthy vs. NF-PitNET tissues demonstrated an increased protein expression and nuclear translocation of KLHL14. Moreover, both E-Cad and KLHL14 shifted from a cytoplasmic (C) form in a low invasive NF-PitNET to a nuclear (N) localization in a high invasive NF-PitNET. A significant correlation was found between E-Cad/KLHL14 co-localization in the cytoplasm (p = 0.01) and nucleus (p = 0.01) and with NF-PitNET invasiveness grade. Conclusions. Nuclear buildup of both E-Cad and KLHL14 detected in high invasive NF-PitNET patients highlights a novel intracellular mechanism governing the tumor propensity to local invasion (Ki67+ ≥ 3%). The prolonged progression-free survival trend documented in patients with lower KLHL14 expression further supported such a hypothesis even if a larger cohort of NF-PitNET patients have to be analyzed to definitively recognize a key prognostic role for KLHL14. [ABSTRACT FROM AUTHOR]

Objective(s): Esophageal cancer stem cells (ECSCs) have been identified as the subset of cells within esophageal squamous cell carcinoma that possess tumorigenic, invasive, and metastatic properties. One important aspect of cancer metastasis is the binding of sialyl-Lewis X (CD15s) with E- or P-selectin, which facilitates the adhesion and migration of cancer cells to distant sites. This study was conducted to investigate the impact of fucosylation processes on the metastatic behavior of ECSCs. Materials and Methods: The esophageal cancer cell line (KYSE-30) was cultured and divided into control and 2F-peracetyl fucose (2F-PerAcFuc) treated groups. Spheres were harvested from these cultures. Cell invasion assay and qPCR were conducted to examine migration and marker expression in both groups. Cancer cell line-derived xenografts were established in nude mice to validate findings in vivo. Results: Our results initially indicated that the addition of 2F-PerAcFuc, an inhibitor of fucosylation, resulted in the down-regulation of the Fut3/CD15s pathway in both cancer stem-like cells and the xenograft model. Measurements of subcutaneous xenograft tumor volume revealed a significant decrease in tumor size among nude mice after treatment with 2F-PerAcFuc. Additionally, a reduction in Fut8/E-cadherin levels was observed in the xenograft model of nude mice. Furthermore, the administration of 2F-PerAcFuc lowered the levels of fucosylated glycoconjugates in nude mice. Conclusion: Our data suggest that inhibition of fucosyltransferase 3 and 8 can reduce the metastatic capacity of cancer stem-like cells by down-regulating CD15s and E-cadherin in a mouse model of esophageal cancer. [ABSTRACT FROM AUTHOR]

Introduction: The characterization of circulating tumor cells (CTC) and circulating tumor microemboli (CTM) has emerged as both a challenge to the standard view of metastasis, and as a valuable means for understanding genotypic and phenotypic variability shown even within the same cancer type. However, in the case of salivary gland neoplasms, limited data are available for the role that CTCs and CTMs play in metastasis and secondary tumor formation.ru.AQ1 In response to this, we propose that similarities between in vitro clusters of cultured salivary gland cancer cells may act as a surrogate model for in vivo CTCs and CTMs isolated from patients. Materials and Methods: Using techniques in immunofluorescence, immunoblotting, and 2-dimensional migration, we isolated and characterized a group of cohort cells from a commercially available cell line (HTB-41). Results: Here, cells exhibited a hybrid phenotype with simultaneous expression of both epithelial and mesenchymal markers (E-cadherin, vimentin, and α-SMA). Cohort cells also exhibited increased migration in comparison to parental cells. Conclusion: Data suggest that these isolated cell clusters may fucntion as a potential in vitro model of CTCs and CTMs. [ABSTRACT FROM AUTHOR]

Laryngeal cancer, particularly the squamous cell carcinoma subtype, is prevalent globally and is characterized by a poor prognosis and high mortality rates. Currently, no definitive prognostic markers exist for predicting the behavior of the tumor. The aim of this study is to examine the correlation between cyclin D1 and E-cadherin expression with some clinicopathological parameters in laryngeal squamous cell carcinoma (LSCC). 60 cases of LSCC were retrospectively studied concerning the clinicopathological features and the potential prognostic role of cyclin D1 and E-cadherin expression in laryngeal carcinoma, using immunohistochemical staining scores on paraffin-embedded cancer tissues from patients who were treated with surgical excision. Reduced Ecadherin expression was significantly correlated with tumor grade (p = 0.0288), T stage (p = 0.041), and lymph node metastasis (p = 0.003). Regarding Cyclin D1, a statistically significant correlation was found with lymph node metastasis (p=0.019). In contrast, cyclin D1 expression was not significantly correlated with TNM stage or tumor grade (p=0.99 and 0.66, respectively). Evaluating expression of cyclin D1 in conjunction with E-cadherin expression in laryngeal squamous cell carcinoma may prove beneficial in identifying patients with lymph node metastasis. Tumor grade, stage, and nodal metastasis can significantly affect E-cadherin expression in patients with LSCC. However, further studies using genetic testing are recommended to assess the role of E-cadherin in tumor progression. [ABSTRACT FROM AUTHOR]

Polyphenols and phenolic acids make up the majority of the complex mixture of compounds, such as grape seed extract (GSE). In this study, the protective effects and working mechanisms of Red Grape Seed extract (GSE) against ethanol (EtOH)-induced tight junction (TJ) and adherent junction protein dysfunction were investigated in the rats' liver, kidney, and spleen. Twenty-four adult Albino Sprague Dawley rats were used and divided into 4 groups: Group 1 (Control Negative), and Group 2 (Control Positive), the rats received a twice-weekly dosage of 40% ethanol; In Group 3, rats were given Red GSE only; Group 4 (treatment group), rats were given EtOH + Red GSE, which was administered three times weekly orally through gavage tube for six weeks. The liver, kidney, and spleen tissue were processed for the H&E staining and Claudin-1, Claudin-5, and E-cadherin biomarkers by IHC analysis. Treatment with Red GSE reduced the histopathologic abnormality scores in the liver (7 vs. 13), kidney (2 vs. 8), and spleen (3 vs. 6) when compared to the EtOH group, which alleviated the harmful effects of EtOH. Additionally, Red GSE increases the expression of Claudin-1, Claudin-5, and E-cadherin by a membrane pattern in the parenchyma of the liver, kidneys, and spleen, mostly by moderate-strong immunostaining in contrast to EtOH, which displayed weak staining in membranous and cytoplasmic regions. Red GSE preserves the tight junction in the damaged cells and is a promising natural agent against ethanol-induced barrier dysfunction. [ABSTRACT FROM AUTHOR]

Although the majority of the population will be protected due to the advent and widespread use of the HPV vaccine, the treatment of cervical cancer for all causes, including HPV-negative cervical cancer, is still worthy of further research. The focal point of this study was Canadine's inhibition of epithelial-mesenchymal transformation (EMT) in cervical cancer. Immunoblotting, wound healing and tumor invasion experiments showed that low concentration of Canadine could inhibit the EMT process, proliferation and migration of HT-3 cells (HPV-negative cell line). Combined with GEO database, it was found that the expression levels of several genes highly expressed in cervical tumor tissues could be inhibited by Canadine, especially MAGEA3. Further experiments confirmed that the inhibition of Canadine on MAGEA3 protein increased with time. The small interference and overexpression plasmid of MAGEA3 were designed and verified. In HT-3 cells, when MAGEA3 levels were directly decreased, mesenchymal phenotypic markers were decreased and epithelial phenotypic markers were increased. The opposite result was obtained by overexpression of MAGEA3. In addition, the inhibition of EMT due to the reduction of endogenous MAGEA3 by Canadine was also offset by the overexpression of exogenous MAGEA3. The study concludes that Canadine inhibits EMT of cervical cancer by inhibiting MAGEA3. [ABSTRACT FROM AUTHOR]

Simple Summary: Epithelial to mesenchymal transition (EMT) programme is central to various cancers, however how this programme applies to glioblastoma, an aggressive primary brain tumor, remains unknown. In particular, the cadherin switch which involves E-cadherin down-regulation and N-cadherin upregulation, is considered a marker of the EMT in epithelial cancers. Given the knowledge gap in the EMT and cadherins expression in GBM, we studied these proteins (E-, P- and N-cadherin) expression in a large cohort of GBM, extensively characterized with clinical, imaging, neuropathological, treatment and survival data. Our results propose that cadherin expression subgroups reflect an EMT-like programme in GBM and predict patient prognosis. Cadherins are cell–cell adhesion proteins which have been strongly implicated in cancer invasion, dissemination and metastasis capacity; thus, they are key players in the epithelial-to-mesenchymal transition (EMT) program. However, their role in glioblastoma (GBM), a primary central nervous system aggressive tumor, remains to be clarified. N-, E- and P-cadherin expression was analyzed on a large series of GBMs, characterized with clinical, imaging and neuropathological parameters, as well as with patients' survival data. In addition, cadherins' expression was studied in match-recurrent cases. Using TCGA data, cadherin expression profiles were also evaluated according to GBM transcription subtypes. N-cadherin expression was observed in 81.5% of GBM, followed by E-cadherin in 31% and P-cadherin in 20.8%. Upon tumor recurrence, P-cadherin was the only significantly upregulated cadherin compared with the primary tumor, being positive in 65.8% of the cases. Actually, P-cadherin gain was observed in 51.4% of matched primary-recurrent cases. Cadherins' co-expression was also explored. Interestingly, E- and N-cadherin co-expression identified a GBM subgroup with frequent epithelial differentiation and a significant survival benefit. On the other hand, subgroups with P-cadherin expression carried the worse prognosis. P- and N-cadherin co-expression correlated with the presence of a mesenchymal phenotype. Expressions of isolated P-cadherin or E- and P-cadherin co-expression were associated with imaging characteristics of aggressiveness, to highly heterogeneous tumors, an d to worse patient survival. Classical cadherins co-expression subgroups present consistent clinical, imaging, neuropathological and survival differences, which probably reflect different states of an EMT-like program in GBM. [ABSTRACT FROM AUTHOR]

Cisplatin is an important platinum drug in cancer chemotherapy in clinical practice. It is well established that the main target of cisplatin is nuclear DNA. However, recent studies have demonstrated that platinum drugs may act on some important functional proteins in the human body. E-cadherin is a newly discovered glycoprotein that has been regarded as an important sign of the occurrence and development of some tumors. This study examines the interactions between cisplatin and E-cadherin by fluorescence spectrometry and atomic force microscopy (AFM). The fluorescence spectrometry results indicated that cisplatin can efficiently quench the fluorescence of E-cadherin. The calculated binding constant Kb was 3.20 × 106 (25 ℃), 1.36 × 106(31 ℃), and 8.22 × 105 L mol−1 (37 ℃). These results reveal that the fluorescence quenching effect of cisplatin on E-cadherin is static quenching. The obtained thermodynamic parameters ΔH < 0, ΔS < 0, and ΔG < 0, indicate that the binding of cisplatin on E-cadherin is a spontaneous process dominated by hydrogen bonds and Van der Waals forces. The AFM results revealed that E-cadherins are interlaced with each other to form a spherical-chain structure. The addition of cisplatin can significantly disrupt the interlaced structure of the E-cadherin molecules. [ABSTRACT FROM AUTHOR]

Background: Worldwide gall bladder cancer (GBC) is known to be the commonest malignant tumour of the biliary tract. It is the most aggressive carcinoma of the biliary tract with short median survival from the time of diagnosis. The aggressive biologic behavior of the carcinoma and non-availability of sensitive screening tests for early detection may be responsible for the poor prognosis associated with GBC. Owing to the delayed diagnosis at an advanced stage, only few of the patients are found to be eligible for a curative surgical resection. Material and Methods: All patients diagnosed with neoplastic and non-neoplastic gallbladder lesions in the Department of Pathology, Subharti Medical College were included in the study between the year 2017-2019. The Hematoxylin and Eosin stained biopsies of 320 patients were assessed and out of them 100 patients were chosen as the sample for the study. The clinicopatholgical data of the 100 patients were compiled into a data base and de-identified. Results: In adenocarcinoma - biliary type, there was positive EGFR expression seen in 64.71% of cases compared to negative expression seen in 35.29% cases, the difference was not statistically significant (p = 0.18). Adenocarcinoma - papillary ype showed positive expression. Adenocarcinoma--intestinal type showed negative EGFR expression, but again, without statistical significance (p = 0.24). Conclusions: The minimal response of advanced cases of GBC to traditional treatments calls for new prognostic and treatment perspectives to be identified. Novel prognostic biomarkers could bring about the needed breakthrough in this regard as they will help in the identification of patients who will benefit tremendously from adjuvant and targeted therapies. [ABSTRACT FROM AUTHOR]

AbstractIntroduction: We investigated the role of E-cadherin and Ber-EP4 in tubal pregnancy by comparing their expressions in epithelial and trophoblastic cells both in ectopic tubal and intrauterine pregnancies. Methods: The Formalin-fixed paraffin embedded blocks of 17 intrauterine and 17 tubal pregnancies were immunohistochemically stained with E-cadherin and Ber-EP4. Results: E-cadherin was expressed in the epithelium, villous and extravillous trophoblast in tubal and intrauterine pregnancies but not in the syncytiotrophoblast. The staining intensity was lower in the extra-villous trophoblast in tubal ectopic pregnancies compared with intrauterine pregnancies. Ber-EP4 was expressed in the epithelium of tubal and intrauterine pregnancies and only in villous cytotrophoblast. The intensity of staining in tubal pregnancy was higher than in intrauterine pregnancy. Discussion: The loss of E-cadherin expression in extra-villous trophoblast and increased expression of Ber-EP4 in the villous cytotrophoblast may play a role in the formation of tubal pregnancy by allowing the blastocyst to attach to the tubal epithelium. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is the most lethal form of pancreatic cancer characterized by therapy resistance and early metastasis, resulting in a low survival rate. Histone deacetylase (HDAC) inhibitors showed potential for the treatment of hematological malignancies. In PDAC, the overexpression of HDAC 2 is associated with the epithelial–mesenchymal transition (EMT), principally accompanied by the downregulation of the epithelial marker E-cadherin and increased metastatic capacity. The effector cytokine transforming growth factor-β (TGF β) is known to be a major inducer of the EMT in PDAC, leading to high metastatic and invasive potential. In addition, the overexpression of HDAC 6 in PDAC is associated with reduced apoptosis. Here, we have demonstrated that a novel HDAC 2/6 inhibitor not only significantly increased E-cadherin expression in PANC-1 cells (5.5-fold) and in 3D PDAC co-culture spheroids (2.5-fold) but was also able to reverse the TGF-β-induced downregulation of E-cadherin expression. Moreover, our study indicates that the HDAC inhibitor mediated re-differentiation resulting in a significant inhibition of tumor cell invasion by approximately 60% compared to control. In particular, we have shown that the HDAC inhibitor induces both apoptosis (2-fold) and cell cycle arrest. In conclusion, the HDAC 2/6 inhibitor acts by suppressing invasion via upregulating E-cadherin mediated by HDAC 2 blockade and by inducing cell cycle arrest leading to apoptosis via HDAC 6 inhibition. These results suggest that the HDAC 2/6 inhibitor might represent a novel therapeutic strategy for the treatment of PDAC tumorigenesis and metastasis. [ABSTRACT FROM AUTHOR]

The development of the optic nerve and its surrounding tissues during the early fetal period is a convoluted period because it spans both the organogenesis period and the fetal period. This study details the microscopic anatomy and histoembryology of the optic nerve in embryos during the early fetal period, including the second half of the first trimester of pregnancy. Serial sections through the orbit of variously aged embryos allowed us to analyze the nerve in both longitudinal and transverse aspects. A histological assessment and description of the structures surrounding and inside the nerve were performed, highlighting the cellular subtypes involved. By employing immunohistochemical techniques, we could characterize the presence and distribution of astrocytes within the optic nerve. Our findings suggest that by the 8th gestational week (WG) the structures are homologs to all the adult ones but with an early appearance so that maturation processes take place afterward. By this age, the axons forming the nerve are definitive adult axons. The glial cells do not yet exhibit adult phenotype, but their aspect becomes adult toward the 13th week. During its development the optic nerve increases in size then, at 14 weeks, it shrinks considerably, possibly through its neural maturation process. The morphological primordium of the blood–nerve barrier can be first noted at 10 WG and at 13 WG the morphological blood–nerve barrier is definitive. The meningeal primordium can be first noted as a layer of agglomerated fibroblasts, later toward 13 WG splitting in pachymeninx and leptomeninges and leaving space for intrinsic blood vessels. [ABSTRACT FROM AUTHOR]

Serratia are opportunistic bacteria, causing infections in plants, insects, animals and humans under certain conditions. The development of bacterial infection in the human body involves several stages of host–pathogen interaction, including entry into non-phagocytic cells to evade host immune cells. The facultative pathogen Serratia proteamaculans is capable of penetrating eukaryotic cells. These bacteria synthesize an actin-specific metalloprotease named protealysin. After transformation with a plasmid carrying the protealysin gene, noninvasive E. coli penetrate eukaryotic cells. This suggests that protealysin may play a key role in S. proteamaculans invasion. This review addresses the mechanisms underlying protealysin's involvement in bacterial invasion, highlighting the main findings as follows. Protealysin can be delivered into the eukaryotic cell by the type VI secretion system and/or by bacterial outer membrane vesicles. By cleaving actin in the host cell, protealysin can mediate the reversible actin rearrangements required for bacterial invasion. However, inactivation of the protealysin gene leads to an increase, rather than decrease, in the intensity of S. proteamaculans invasion. This indicates the presence of virulence factors among bacterial protealysin substrates. Indeed, protealysin cleaves the virulence factors, including the bacterial surface protein OmpX. OmpX increases the expression of the EGFR and β1 integrin, which are involved in S. proteamaculans invasion. It has been shown that an increase in the invasion of genetically modified S. proteamaculans may be the result of the accumulation of full-length OmpX on the bacterial surface, which is not cleaved by protealysin. Thus, the intensity of the S. proteamaculans invasion is determined by the balance between the active protealysin and its substrate OmpX. [ABSTRACT FROM AUTHOR]

Loss of the cell–cell adhesion protein E‐cadherin underlies the development of diffuse‐type gastric cancer (DGC), which is characterized by the gradual accumulation of tumor cells originating from the gastric epithelium in the surrounding stroma. How E‐cadherin deficiency drives DGC formation remains elusive. Therefore, we investigated the consequences of E‐cadherin loss on gastric epithelial organization utilizing a human gastric organoid model and histological analyses of early‐stage DGC lesions. E‐cadherin depletion from gastric organoids recapitulates DGC initiation, with progressive loss of a single‐layered architecture and detachment of individual cells. We found that E‐cadherin deficiency in gastric epithelia does not lead to a general loss of epithelial cohesion but disrupts the spindle orientation machinery. This leads to a loss of planar cell division orientation and, consequently, daughter cells are positioned outside of the gastric epithelial layer. Although basally delaminated cells fail to detach and instead reintegrate into the epithelium, apically mispositioned daughter cells can trigger the gradual loss of the single‐layered epithelial architecture. This impaired architecture hampers reintegration of mispositioned daughter cells and enables basally delaminated cells to disseminate into the surrounding matrix. Taken together, our findings describe how E‐cadherin deficiency disrupts gastric epithelial architecture through displacement of dividing cells and provide new insights in the onset of DGC. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Abstract Transmembrane protein 52B (TMEM52B), a newly identified tumor‐related gene, has been reported to regulate various tumors, yet its role in nasopharyngeal carcinoma (NPC) remains unclear. Transcriptomic analysis of NPC cell lines reveals frequent overexpression of TMEM52B, and immunohistochemical results show that TMEM52B is associated with advanced tumor stage, recurrence, and decreased survival time. Depleting TMEM52B inhibits the proliferation, migration, invasion, and oncogenesis of NPC cells in vivo. TMEM52B encodes two isoforms, TMEM52B‐P18 and TMEM52B‐P20, differing in their N‐terminals. While both isoforms exhibit similar pro‐oncogenic roles and contribute to drug resistance in NPC, TMEM52B‐P20 differentially promotes metastasis. This functional discrepancy may be attributed to their distinct subcellular localization; TMEM52B‐P18 is confined to the cytoplasm, while TMEM52B‐P20 is found both at the cell membrane and in the cytoplasm. Mechanistically, cytoplasmic TMEM52B enhances AKT phosphorylation by interacting with phosphoglycerate kinase 1 (PGK1), fostering NPC growth and metastasis. Meanwhile, membrane‐localized TMEM52B‐P20 promotes E‐cadherin ubiquitination and degradation by facilitating its interaction with the E3 ubiquitin ligase NEDD4, further driving NPC metastasis. In conclusion, the TMEM52B‐P18 and TMEM52B‐P20 isoforms promote the metastasis of NPC cells through different mechanisms. Drugs targeting these TMEM52B isoforms may offer therapeutic benefits to cancer patients with varying degrees of metastasis.

Purpose: Previous studies have reported that miR-30d-5p gene expression can inhibit tumor proliferation, but its mechanism has not been fully elucidated. Methods: Based on previous findings, TGF-β1 was used to induce epithelial mesenchymal transformation in A549 cells. The expression levels of DUSP-1, E-cadherin and Vimentin were detected by Western blot. mRNA expression levels of DUSP-1, E-cadherin and Vimentin were determined by RT-qPCR. The expression level of miR-30d-5p was determined by RT-qPCR. Results: The induction effect of TGF-β1 could be reversed by the intervention of miR-30d-5p in A549 cells. miRNA inhibition experiment showed that miR-30d-5p inhibitor could effectively inhibit the expression of miR-30d-5p in A549 cells. After miR-30d-5p intervention, TGF-β1 was reversed on EMT-related genes (Dusp-1, E-cadherin, Vimentin). Conclusion: TGF-β1 can induce epithelial mesenchymal transformation of A549 cells, and miR-30d-5p may be a key regulatory mechanism in regulating gene and protein expression of TGF-β1-mediated DUSP-1, E-cadherin and Vimentin. This provides a new perspective for understanding the anti-tumor effect of miR-30d-5p gene.

Background and aims: Cadherins are adhesion proteins, and their dysregulation may result in the development of atherosclerosis, plaque rupture, or lesions of the vascular wall. The aim of the present study was to detect the associations of cadherins-P, −E, and H, with atherosclerosis and pathological cardiovascular conditions. Methods and results: The present study with 3-year follow up evaluated atherosclerosis and fasting levels of P-, E-, and H-cadherins in the serum samples of 214 patients in a hospital setting. Coronary lesions were assessed by coronary angiography as Gensini score. Serum proteomic profiling was performed using antibody microarrays. The contents of P-, E-, and H-cadherins in the serum were measured using indirect ELISA. High levels of P- and E-cadherins and low levels of H-cadherin were associated with severity of atherosclerosis. High levels of P- and E-cadherins were associated with higher incidence of nonfatal cardiovascular outcomes. E-cadherin was associated with higher incidence of recurrent revascularization during 3 year follow-up. The results of Spearman rank correlation analysis revealed various associations of the three cadherins with lipid, endothelial, and metabolic biomarkers. Conclusions: The data indicated that classical and atypical cadherins were associated with atherosclerosis progression. Elevated levels of P-cadherin were associated with coronary atherosclerosis. The data indicated that various lipid, endothelial, and metabolic biomarkers may influence the levels of cadherins. Thus, P-, E-, and H-cadherins may be promising markers for the assessment of cardiovascular risk.