Antonio Celentano

This critical review examines whether and how disruption of epithelial barrier function—with a particular focus on hemidesmosomal remodelling, polarity regulators and basement membrane integrity—contributes to the initiation and progression of squamous cell carcinoma (SCC). We synthesise multidisciplinary evidence from molecular studies, immunohistochemistry, spatial profiling and experimental models, and highlight stage-specific patterns of adhesion and polarity change from normal epithelium through dysplasia to invasive disease. The assembled data indicate that selective remodelling of cell–matrix and cell–cell adhesion can reprogramme intracellular signalling, promote epithelial plasticity (including partial EMT), and facilitate collective modes of invasion while reshaping stromal and immune microenvironments. Empirical findings discussed include stage-associated changes in hemidesmosomal protein expression and architectural features that track with malignant risk, as well as mechanistic studies linking hemidesmosome disassembly to focal adhesion signalling. We conclude that disrupted epithelial organisation can act as a disease-modifying factor in SCC and that further mechanistic, spatial and longitudinal studies are needed to establish causality and to assess whether restoration of barrier integrity or targeting of resulting vulnerabilities has therapeutic or prognostic value.

Fucoidan, a sulphated polysaccharide from brown seaweeds, has proposed anti-inflammatory and immunomodulatory properties. Clinical evidence suggests potential benefits, but remains limited, heterogeneous and inconsistent.

Background: RANTES, a chemokine involved in regulating inflammatory responses, has been implicated in the pathogenesis of various diseases, including oral lichen planus (OLP). In this condition, the interaction between C–C motif ligand 5 (CCL5) and CC motif chemokine receptor 5 (CCR5) may contribute to the destruction of basal keratinocytes and an imbalance of Th1 cells, leading to chronic inflammation. Objectives: This systematic review aimed to evaluate expression of the CCL5 in the serum and relevant cell types of patients with oral lichen planus and oral lichenoid lesions (OLLs) compared to controls. Methods: We searched the following databases: Medline (Ovid), CENTRAL (Cochrane Library), Embase (Ovid), CINAHL (EBSCO), and Web of Science Core Collection, up to May 2026. Study quality and risk of bias were assessed using the Joana Briggs Institute tools. Results: Five studies (227 participants) met the inclusion criteria. The findings indicated a marked upregulation of CCL5 in the serum, T‐lymphocytes, and fibroblasts of OLP/OLL patients compared to controls. However, these results were weakened by high risk of bias in statistical analysis, reporting, and confounding factors, along with significant heterogeneity in methodology and diagnostic criteria. Conclusion: CCL5 may play a role in the pathogenesis of OLP/OLLs by promoting T‐cell infiltration, correlating positively with disease severity, and presenting itself as a potential therapeutic target. However, the low‐quality evidence due to the high risk of bias identified in the majority of included studies highlights the need for further research to confirm the immunomodulatory role of CCL5 in OLP/OLLs pathogenesis.

Gonorrhoea, a sexually transmitted infection caused by Neisseria gonorrhoeae (NG), represents a significant public health concern, with at least 82 million new cases among adolescents and adults an...

Background: Oral squamous cell carcinoma (OSCC) is the most common malignancy of the head and neck, associated with substantial morbidity and mortality worldwide. Oral epithelial dysplasia (OED) can precede OSCC, offering a critical window for preventive and therapeutic intervention. This review maps the historical and current landscape of in vitro and in vivo models of OED, providing insight into their strengths, limitations, and translational relevance. Methods: A systematic review and temporal analysis were conducted following PRISMA guidelines, with literature searches performed across Medline, EMBASE, EBM Reviews, and Web of Science. Results: From 4009 records, 292 studies from 26 countries were included, yielding 307 models of OED. Only a minority of studies (17.4%) focused primarily on dysplasia as a precancerous condition. In vivo models predominated (88.9%), while in vitro systems were comparatively scarce and largely limited to 2D cultures. Organoid‐based approaches were rarely reported, highlighting a gap in advanced model development. Reproducibility data were available for 125 studies (45.8%). The hamster emerged as the most frequently used animal [ n = 96, 35%], and 4‐nitroquinoline‐1‐oxide (4‐NQO) remained the most common carcinogen, particularly in murine models. A strong sex bias was observed, with male animals heavily over‐represented. Conclusion: Overall, models of OED remain under‐represented and under‐developed, particularly in comparison to innovations in other fields of cancer research. Despite the central role of OED in oral carcinogenesis, current models do not adequately reflect clinical diversity or exploit modern 3D and patient‐derived technologies. This review provides a critical reference point to guide future studies toward more accurate, reproducible, and clinically relevant models, with the potential to advance prevention, early detection, and targeted therapies for OSCC.

Background: Hemidesmosomal subunits have gained attention for their potential role in the progression of oral squamous cell carcinoma (OSCC). However, formal analysis of quantitative expression patterns correlating with OSCC disease pathogenesis remains limited. This study evaluated the expression of key yet overlooked hemidesmosomal subunits, plectin isoform Ia (PIa), dystonin, and CD151 antigen, from normal tissue as well as tissue from hyperplasia, dysplasia, and OSCC in the human and murine oral cavity. Methods: Immunohistochemistry was performed on custom‐built human tissue microarrays and 4‐Nitroquinoline 1‐oxide (4‐NQO)‐induced murine OSCC covering the spectrum of histological changes from normal to cancer. Quantitative image analysis of subunit expression was conducted using QuPath, with distinct analytical approaches applied to human tissues, including a refined method focusing on the basement membrane zone (BMZ) and adjacent basal epithelial layers, key sites of hemidesmosomal protein localization. Results: A significant increase in expression of all three proteins was observed comparing normal tissue with hyperplasia, dysplasia, and OSCC in murine tissues, but not in humans. The expression of hemidesmosomal proteins increased across this spectrum, suggesting their potential as progression biomarkers in mice. A focused analysis of the basement membrane zone and adjacent basal epithelial layers in human tissues revealed a sustained baseline expression and a significant reduction in CD151 antigen in OSCC compared with control and high‐grade dysplasia groups, as well as a significant reduction in dystonin expression in OSCC compared to high‐grade dysplasia. Conclusion: Our findings highlight the importance of biologically targeted region‐of‐interest selection when assessing hemidesmosomal protein expression in OSCC while demonstrating that BMZ‐focused digital analysis provides a more informative approach for exploratory evaluation of heterogeneous human tissues alongside progression‐associated patterns observed in a murine model.

Objectives: The global rise in Neisseria gonorrhoeae (NG) infections, particularly oropharyngeal cases, drives treatment failures from antibiotic resistance. However, infection dynamics within oropharyngeal sites remain unclear. We developed an in vitro model using three human oropharyngeal epithelial cells to investigate infection dynamics and evaluate treatment strategies. Methods: Tonsillar, floor of mouth (FOM) and gingival cell lines were infected with NG strains: antimicrobial-susceptible FA1090 and antimicrobial-resistant WHO-R. Oral commensal Neisseria oralis served as a bacterial negative control. Infected cells were treated with antibiotics known to cure NG strains (ie, ciprofloxacin/azithromycin/ceftriaxone/cefixime) and an antimicrobial negative control that does not cure NG strains (ie, tetracycline) at 1×, 2× and 3× the minimum inhibitory concentration for 30, 60 and 120 min. Post-treatment, cells were treated with gentamicin to eliminate extracellular bacteria, lysed and internalised NG quantified. Results: NG invasion for both strains was highest in tonsillar cells and lowest in FOM cells. Gingival cells only demonstrated high invasion by FA1090. Validation experiments confirmed FA1090 clearance was highest with azithromycin, ceftriaxone and ciprofloxacin, while cefixime and tetracycline showed variable efficacy. No tested antibiotics cleared WHO-R from all cell lines. Gentamicin consistently failed to clear infections. There was minimal invasion of N. oralis across all cell lines. Conclusions: NG demonstrates site-specific and strain-specific invasion of oral cells, targeting tonsils and gingiva. The model’s validity is supported by drug efficacy results aligning with clinical data and limited invasion by N. oralis . This model provides a basis for developing a three-dimensional system to better understand oropharyngeal NG infections and identify and evaluate novel treatments.

Objectives: Characterize LncUCA1 expression in OSCC cancer‐associated fibroblasts (CAFs), investigate immune regulation by high LncUCA1 CAFs, and assess their impact on tumor malignancy in vitro.Materials and Methods: Transcriptome sequencing identified upregulated genes in matched CAFs and normal fibroblasts (NFs) from OSCC patients. Clinical outcomes were evaluated in 21 OSCC patients. LncUCA1's effect on PD‐L1 expression in CAFs was assessed by flow sorting and qRT‐PCR. Co‐culture experiments evaluated CAFs' impact on CD8⁺ T cell proliferation and immunosuppression. Matrigel contraction and CCK8 assays explored CAFs' matrix contraction and proliferation. Direct co‐culture analyzed CAFs' effect on OSCC proliferation. Transwell assays examined CAFs' impact on tumor cell migration and invasion.Results: LncUCA1 was significantly upregulated in CAFs compared to NFs. Higher LncUCA1 expression correlated with advanced tumor stage and shorter overall survival. LncUCA1 positively correlated with PD‐L1 expression and activated the JAK2/STAT3 pathway in CAFs. Co‐culture experiments showed high LncUCA1 CAFs inhibited CD8⁺ T cell proliferation and enhanced immunosuppression. LncUCA1 overexpression enhanced matrix contraction but significantly promoted proliferation, migration, and invasion of OSCC cells.Conclusions: LncUCA1 upregulation in CAFs drives PD‐L1 expression, inhibits CD8⁺ T cell proliferation, and promotes immunosuppression. High LncUCA1 CAFs also enhance OSCC proliferation, migration, and invasion.

Objective: In this overview, we present compelling evidence from multiple systematic reviews and meta-analyses (SRMAs) and examine the prognostic role of the PD-L1/PD-1 axis, as well as the potential of personalized treatment strategies targeting this axis, in patients with oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs). Methods: Six databases were searched to retrieve systematic review and meta-analysis studies. The population of interest was patients with OSCC and OPMDs in whom the expression of PD-L1 and PD-1 had been investigated. At least one of the following outcomes was reported, along with at least one clinicopathological feature: overall survival, disease-free survival, or disease-specific survival. All studies were assessed for risk of bias using the AMSTAR 2 tool. Results: A total of 195 studies were found through the initial search, and after duplicate removal, 97 studies were screened by title and Finally, five systematic reviews and meta-analysis studies fit our inclusion criteria and were included in this review. Conclusions: Based on two published systematic reviews, our study revealed a lack of evidence for the prognostic value of PD-L1 in improving overall survival in oral cancer patients. However, it showed a correlation with specific clinicopathological features such as sex, lymph node metastasis, and HPV status.

Background: Oral squamous cell carcinoma (OSCC) represents a significant global oral health concern. Non‐anticoagulant heparin (NH) emerges as a promising solution considering the enhanced survival observed with anticoagulants in cancer treatment. Methods: We used the MTS assay (0/24/48/72 h), scratch assay (MuviCyte, 0–18 h), invasion Matrigel (24 h), and cytotoxic assay (0–24 h) to assess the in vitro effects of NH and heparin (10, 20, 40, 80 U/mL) on three oral human cell lines (H400/H357/OKF6) as well as their ability to interfere with the chemotherapeutic agents 5FU and cisplatin (1–5 μg/mL). Results: Remarkably, NH not only significantly induced a significant cytotoxic effect on both cancer cell lines at 80 U/mL but also inhibited proliferation at 48/72 h to a comparable extent as heparin. Notably, neither drug exhibited cytotoxic effects on the normal cells. Furthermore, in H400/H357 cells, both heparin and NH significantly inhibit the cell migration and invasion rate. Importantly, the combination of these drugs with commonly used chemotherapeutic agents for OSCC treatment did not compromise their efficacy against the tested cell lines. Conclusion: NH demonstrates promising potential without compromising the efficacy of commonly used chemotherapeutic agents. These results underscore the need for the translation of this research to preclinical animal models.