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Saliva is crucial in maintaining oral health; its composition reflects the body's physiological and diseased state. Among salivary components, antimicrobial peptides (AMPs) stand out for their broad antimicrobial activities and role in modulating the oral microbiota and innate immune response. Local and systemic diseases can affect the levels of AMPs in saliva, making them attractive biomarkers. However, the large variability in their concentrations hampers their use in diagnostics. Knowledge of the various factors influencing the profile of salivary AMPs is essential for their use as biomarkers. Here, we examine how lifestyle factors such as physical activity, dietary supplementation, tobacco smoking, and psychological stress impact salivary AMP levels. By understanding these sources of variability, we can take a step forward in using AMPs for diagnostics and prognostics and develop new tailored and preventative approaches. [ABSTRACT FROM AUTHOR]

Simple Summary: Ochratoxin A (OTA) present in food products poses a serious threat to health due to its wide spectrum of effects, including genotoxicity, nephrotoxicity, neurotoxicity, embryotoxicity, teratogenicity, and immunosuppression. Moreover, it is associated with carcinogenesis, as a result of which it has been classified as a potential human carcinogen. In this review, literature reports on the correlations between carcinogenesis and OTA, with particular emphasis on certain organs such as the kidney or digestive system organs and the cancers associated with them, are gathered. Furthermore, we describe the potential mechanisms underlying OTA-induced carcinogenesis and discuss existing limitations. Background: Ochratoxin A (OTA) is widely recognized for its broad spectrum of toxic effects and is classified as a potential human carcinogen, placed in group 2B by the International Agency for Research on Cancer (IARC). Its presence in food and beverages poses a significant health hazard. Extensive research has documented the efficient absorption and distribution of OTA throughout the body via the bloodstream and tissues, underscoring the associated health risk. Additionally, ongoing studies aim to clarify the link between OTA exposure and carcinogenesis. The obtained results indicate a strong correlation between OTA and renal cell carcinoma (RCC), with potential associations with other malignancies, including hepatocellular carcinoma (HCC), gallbladder cancer (GBC), and squamous cell carcinoma (SCC). OTA is implicated in oxidative stress, lipid peroxidation, apoptosis, DNA damage, adduct formation, miRNA deregulation, and distributions in the cell cycle, all of which may contribute to carcinogenesis. Conclusions: Despite significant research efforts, the topic remains inexhaustible and requires further investigation. The obtained results do not yield definitive conclusions, potentially due to species-specific differences in the animal models used and challenges in extrapolating these results to humans. In our review, we delve deeper into the potential mechanisms underlying OTA-induced carcinogenesis and discuss existing limitations, providing directions for future research. [ABSTRACT FROM AUTHOR]

Iron is an essential element for human health. In humans, dysregulated iron homeostasis can result in a variety of disorders and the development of cancers. Enhanced uptake, redistribution, and retention of iron in cancer cells have been suggested as an "iron addiction" pattern in cancer cells. This increased iron in cancer cells positively correlates with rapid tumor growth and the epithelial-to-mesenchymal transition, which forms the basis for tumor metastasis. However, the source of iron and the mechanisms cancer cells adopt to actively acquire iron is not well understood. In the present study, we report, for the first time, that the peptide hormone, prolactin, exhibits a novel function in regulating iron distribution, on top of its well-known pro-lactating role. When stimulated by prolactin, breast cancer cells increase CD44, a surface receptor mediating the endocytosis of hyaluronate-bound iron, resulting in the accumulation of iron in cancer cells. In contrast, macrophages, when treated by prolactin, express more ferroportin, the only iron exporter in cells, giving rise to net iron output. Interestingly, when co-culturing macrophages with pre-stained labile iron pools and cancer cells without any iron staining, in an iron free condition, we demonstrate direct iron flow from macrophages to cancer cells. As macrophages are one of the major iron-storage cells and it is known that macrophages infiltrate tumors and facilitate their progression, our work therefore presents a novel regulatory role of prolactin to drive iron flow, which provides new information on fine-tuning immune responses in tumor microenvironment and could potentially benefit the development of novel therapeutics. [ABSTRACT FROM AUTHOR]

Simple Summary: We present in this study novel data which demonstrates that the most common type of tumor of the salivary glands may be accurately diagnosed using a specific type of radiological imaging. This may be used to help discriminate this tumor or recurrent versions of it amid various types of benign and malignant tumors. Furthermore, this data suggest that new avenues of minimally invasive therapy may be viable for these tumors and potentially even malignant versions of these tumors and should be examined in further studies. Introduction: Currently, the diagnosis of salivary gland tumors using imaging techniques is unreliable. Methods: In this monocentric retrospective study, we examined patients who received a 68Ga-DOTATOC PET/CT and subsequently underwent a salivary gland tumor resection between 1 January 2010 and 31 December 2021. PET/CT image assessment was compared with somatostatin receptor (SSTR) expression and histology. Results: Thirteen patients (five pleomorphic adenoma (PA) and eight other parotid lesions (OPL)) received a 68Ga-DOTATOC PET/CT. Imaging displayed strong focal tracer uptake in all PA except for one with strong tumor to background discrimination. PA revealed higher SUVmax, SUVmean, liver and blood pool quotients than those of Warthin tumors (WT) and of OPL. In comparison to the contralateral parotid, SUVmax (p = 0.02), SUVmean (p = 0.02), liver quotient (p = 0.03) and blood pool quotient (p = 0.03) were all significantly higher. In contrast, WT and OPL showed in relation to the contralateral parotid no significant differences of SUVmax (WT p = 0.79; OPL p = 0.11), SUVmean (WT p = 1.0; OPL p = 0.08), liver quotient (WT p = 0.5; OPL p = 0.08) and blood pool quotient (WT p = 0.8; OPL p = 0.19). Two PA and one granuloma were not available for examination. In the immunohistochemal analysis, all PA demonstrated the highest intensity of SSTR2 expression (grade 3). Furthermore, PA had a high percentage of cells expressing SSTR2 (20%, 80% and 55%). Conclusions: A strong tracer uptake in PA was shown in 68Ga-DOTATOC PET/CT. This may allow physicians to utilize radioligated somatostatin analogue PET CT/MR imaging to accurately diagnose PA. Additionally, it may be possible in the future to treat the PA with a noninvasive peptide receptor radionuclide therapy or with somatostatin analogues. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) presents unique challenges and opportunities for treatment, particularly regarding de-escalation strategies to reduce treatment morbidity without compromising oncological outcomes. This paper examines the role of Transoral Robotic Surgery (TORS) as a de-escalation strategy in managing HPV-related OPSCC. We conducted a comprehensive literature review from January 2010 to June 2023, focusing on studies exploring TORS outcomes in patients with HPV-positive OPSCC. These findings highlight TORS's potential to reduce the need for adjuvant therapy, thereby minimizing treatment-related side effects while maintaining high rates of oncological control. TORS offers advantages such as precise tumor resection and the ability to obtain accurate pathological staging, which can guide the tailoring of adjuvant treatments. Some clinical trials provide evidence supporting the use of TORS in specific patient populations. The MC1273 trial demonstrated promising outcomes with lower doses of adjuvant radiotherapy (RT) following TORS, showing high locoregional tumor control rates and favorable survival outcomes with minimal side effects. ECOG 3311 evaluated upfront TORS followed by histopathologically directed adjuvant therapy, revealing good oncological and functional outcomes, particularly in intermediate-risk patients. The SIRS trial emphasized the benefits of upfront surgery with neck dissection followed by de-escalated RT in patients with favorable survival and excellent functional outcomes. At the same time, the PATHOS trial examined the impact of risk-adapted adjuvant treatment on functional outcomes and survival. The ongoing ADEPT trial investigates reduced-dose adjuvant RT, and the DART-HPV study aims to compare standard adjuvant chemoradiotherapy (CRT) with a reduced dose of adjuvant RT in HPV-positive OPSCC patients. These trials collectively underscore the potential of TORS in facilitating treatment de-escalation while maintaining favorable oncological and functional outcomes in selected patients with HPV-related OPSCC. The aim of this scoping review is to discuss the challenges of risk stratification, the importance of HPV status determination, and the implications of smoking on treatment outcomes. It also explores the evolving criteria for adjuvant therapy following TORS, focusing on reducing radiation dosage and volume without compromising treatment efficacy. In conclusion, TORS emerges as a viable upfront treatment option for carefully selected patients with HPV-positive OPSCC, offering a pathway toward treatment de-escalation. However, selecting the optimal candidate for TORS-based de-escalation strategies is crucial to fully leverage the benefits of treatment de-intensification. [ABSTRACT FROM AUTHOR]

Simple Summary: Intrahepatic cholangiocarcinoma (ICCA) is the second most common type of primary liver malignancy after hepatocellular carcinoma (HCC). ICCA is characterized by molecular heterogeneity and a diverse histopathological spectrum. Generally, the prognosis for patients diagnosed with ICCA is poor. Recent advances have improved our understanding of the molecular genetics and histological subtypes of ICCA. An accurate diagnosis of ICCA is important for patient management and prognosis. This review aims to provides an updated overview of the pathology of ICCA, with a particular focus on its molecular genetics, histological subtypes, and the diagnostic approaches necessary to distinguish it from other diseases. Intrahepatic cholangiocarcinoma (ICCA) is a malignant epithelial neoplasm characterized by biliary differentiation within the liver. ICCA is molecularly heterogeneous and exhibits a broad spectrum of histopathological features. It is a highly aggressive carcinoma with high mortality and poor survival rates. ICCAs are classified into two main subtypes: the small-duct type and large-duct types. These two tumor types have different cell origins and clinicopathological features. ICCAs are characterized by numerous molecular alterations, including mutations in KRAS, TP53, IDH1/2, ARID1A, BAP1, BRAF, SAMD4, and EGFR, and FGFR2 fusion. Two main molecular subtypes—inflammation and proliferation—have been proposed. Recent advances in high-throughput assays using next-generation sequencing have improved our understanding of ICCA pathogenesis and molecular genetics. The diagnosis of ICCA poses a significant challenge for pathologists because of its varied morphologies and phenotypes. Accurate diagnosis of ICCA is essential for effective patient management and prognostic determination. This article provides an updated overview of ICCA pathology, focusing particularly on molecular features, histological subtypes, and diagnostic approaches. [ABSTRACT FROM AUTHOR]

Oral potentially malignant disorders (OPMDs) are precursors to over 80% of oral cancers. Hematoxylin and eosin (H&E) staining, followed by pathologist interpretation of tissue and cellular morphology, is the current gold standard for diagnosis. However, this method is qualitative, can result in errors during the multi-step diagnostic process, and results may have significant inter-observer variability. Chemical imaging (CI) offers a promising alternative, wherein label-free imaging is used to record both the morphology and the composition of tissue and artificial intelligence (AI) is used to objectively assign histologic information. Here, we employ quantum cascade laser (QCL)-based discrete frequency infrared (DFIR) chemical imaging to record data from oral tissues. In this proof-of-concept study, we focused on achieving tissue segmentation into three classes (connective tissue, dysplastic epithelium, and normal epithelium) using a convolutional neural network (CNN) applied to three bands of label-free DFIR data with paired darkfield visible imaging. Using pathologist-annotated H&E images as the ground truth, we demonstrate results that are 94.5% accurate with the ground truth using combined information from IR and darkfield microscopy in a deep learning framework. This chemical-imaging-based workflow for OPMD classification has the potential to enhance the efficiency and accuracy of clinical oral precancer diagnosis. [ABSTRACT FROM AUTHOR]

Lactoferrins and lactoferrin-derived peptides display numerous functions linked to innate immunity in mammalians, spanning from antimicrobial to anti-inflammatory and immunomodulatory actions, and even demonstrate antitumor properties. To date, the proposed mechanisms for their biological actions are varied, although the molecular basis that governs lactoferrin interactions with molecular targets has been clarified only in a limited number of specific cases. However, key in silico methods have recently moved the topic to the fore, thus greatly expanding the possibilities of large-scale investigations on macromolecular interactions involving lactoferrins and their molecular targets. This review aims to summarize the current knowledge on the structural determinants that drive lactoferrin recognition of molecular targets, with primary focus on the mechanisms of activity against bacteria and viruses. The understanding of the structural details of lactoferrins' interaction with their molecular partners is in fact a crucial goal for the development of novel pharmaceutical products. [ABSTRACT FROM AUTHOR]

Odontogenic keratocyst (OK) is a benign intraosseous cystic lesion characterized by a parakeratinized stratified squamous epithelial lining with palisade basal cells. It represents 10–12% of odontogenic cysts. The changes in its classification as a tumor or cyst have increased interest in its pathogenesis. Objective: Identify key genes in the pathogenesis of sporadic OK through in silico analysis. Materials and methods: The GSE38494 technical sheet on OK was analyzed using GEOR2. Their functional and canonical signaling pathways were enriched in the NIH-DAVID bioinformatic platform. The protein–protein interaction network was constructed by STRING and analyzed with Cytoscape-MCODE software v 3.8.2 (score > 4). Post-enrichment analysis was performed by Cytoscape-ClueGO. Results: A total of 768 differentially expressed genes (DEG) with a fold change (FC) greater than 2 and 469 DEG with an FC less than 2 were identified. In the post-enrichment analysis of upregulated genes, significance was observed in criteria related to the organization of the extracellular matrix, collagen fibers, and endodermal differentiation, while the downregulated genes were related to defensive response mechanisms against viruses and interferon-gamma activation. Conclusions. Our in silico analysis showed a significant relationship with mechanisms of extracellular matrix organization, interferon-gamma activation, and response to viral infections, which must be validated through molecular assays. [ABSTRACT FROM AUTHOR]

Background: In metastatic breast cancer (MBC), [18F]fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) can be used for staging. We evaluated the correlation between BC histopathological characteristics and [18F]FDG uptake in corresponding metastases. Patients and Methods: Patients with non-rapidly progressive MBC of all subtypes prospectively underwent a baseline histological metastasis biopsy and [18F]FDG-PET. Biopsies were assessed for estrogen, progesterone, and human epidermal growth factor receptor 2 (ER, PR, HER2); Ki-67; and histological subtype. [18F]FDG uptake was expressed as maximum standardized uptake value (SUVmax) and results were expressed as geometric means. Results: Of 200 patients, 188 had evaluable metastasis biopsies, and 182 of these contained tumor. HER2 positivity and Ki-67 ≥ 20% were correlated with higher [18F]FDG uptake (estimated geometric mean SUVmax 10.0 and 8.8, respectively; p = 0.0064 and p = 0.014). [18F]FDG uptake was lowest in ER-positive/HER2-negative BC and highest in HER2-positive BC (geometric mean SUVmax 6.8 and 10.0, respectively; p = 0.0058). Although [18F]FDG uptake was lower in invasive lobular carcinoma (n = 31) than invasive carcinoma NST (n = 146) (estimated geometric mean SUVmax 5.8 versus 7.8; p = 0.014), the metastasis detection rate was similar. Conclusions: [18F]FDG-PET is a powerful tool to detect metastases, including invasive lobular carcinoma. Although BC histopathological characteristics are related to [18F]FDG uptake, [18F]FDG-PET and biopsy remain complementary in MBC staging (NCT01957332). [ABSTRACT FROM AUTHOR]

Simple Summary: Lichen planus (LP) is a chronic inflammatory mucocutaneous disease of autoimmune nature and unknown etiology, which can affect the oral mucosa, skin, nails, scalp, genitalia, and other mucous membranes. The anatomical location most frequently affected by LP is the oral cavity—called oral lichen planus (OLP)—where white reticular lesions may also be accompanied by erosive, atrophic, bullous, papular, or plaque lesions. The most important feature of OLP is its capacity to develop into oral cancer throughout the course of the disease, which is why OLP is currently recognized as an oral potentially malignant disorder (OPMD). New primary-level studies (n = 20; 11,512 patients suffering from OLP or related lesions) have been published in the last 5 years on this topic. In the present meta-analysis, we provide an updated OLP malignant transformation ratio, which is higher than what was previously reported; resolve some remaining controversies; and provide new recommendations for clinical practice in the management of OLP patients. A systematic review and a meta-analysis is presented on published articles on the malignant transformation of oral lichen planus (OLP) and related conditions, which, based on current evidence, updates an earlier systematic review published by our research group that included publications until November 2018. In this updated study (Nov-2023) we searched MEDLINE, Embase, Web of Science, and Scopus. We evaluated the methodological quality of studies (QUIPS tool) and carried out meta-analyses. The inclusion criteria were met by 101 studies (38,083 patients), of which, 20 new primary-level studies (11,512 patients) were published in the last 5 years and were added to our updated study. The pooled malignant transformation ratio was 1.43% (95% CI = 1.09–1.80) for OLP; 1.38% (95% CI = 0.16–3.38) for oral lichenoid lesions; 1.20% (95% CI = 0.00–4.25) for lichenoid reactions; and 5.13% (95% CI = 1.90–9.43) for OLP with dysplasia. No significant differences were found between the OLL or LR groups and the OLP subgroup (p = 0.853 and p = 0.328, respectively), and the malignant transformation was significantly higher for the OLP with dysplasia group in comparison with the OLP group (p = 0.001). The factors that had a significant impact with a higher risk of malignant transformation were the presence of epithelial dysplasia, a higher methodological quality, the consumption of tobacco and alcohol, the location of lesions on the tongue, the presence of atrophic and erosive lesions, and infection by the hepatitis C virus. In conclusion, OLP behaves as an oral potentially malignant disorder (OPMD), whose malignancy ratio is probably underestimated as a consequence essentially of the use of inadequate diagnostic criteria and the low methodological quality of the studies on the subject. [ABSTRACT FROM AUTHOR]

The use of mRNA-based immunotherapies that leverage the genomes of oncolytic viruses holds significant promise in addressing glioblastoma (GBM), an exceptionally aggressive neurological tumor. We explore the significance of mRNA-based platforms in the area of immunotherapy, introducing an innovative approach to mitigate the risks associated with the use of live viruses in cancer treatment. The ability to customize oncolytic virus genome sequences enables researchers to precisely target specific cancer cells, either through viral genome segments containing structural proteins or through a combination of regions with oncolytic potential. This strategy may enhance treatment effectiveness while minimizing unintended impacts on non-cancerous cells. A notable case highlighted here pertains to advanced findings regarding the application of the Zika virus (ZIKV) in GBM treatment. ZIKV, a member of the family Flaviviridae, shows oncolytic properties against GBM, opening novel therapeutic avenues. We explore intensive investigations of glioblastoma stem cells, recognized as key drivers in GBM initiation, progression, and resistance to therapy. However, a comprehensive elucidation of ZIKV's underlying mechanisms is imperative to pave the way for ZIKV-based clinical trials targeting GBM patients. This investigation into harnessing the potential of oncolytic-virus genomes for mRNA-based immunotherapies underscores its noteworthy implications, potentially paving the way for a paradigm shift in cancer treatment strategies. [ABSTRACT FROM AUTHOR]

Myeloperoxidase (MPO) is a heme-containing peroxidase, mainly expressed in neutrophils and, to a lesser extent, in monocytes. MPO is known to have a broad bactericidal ability via catalyzing the reaction of Cl− with H2O2 to produce a strong oxidant, hypochlorous acid (HOCl). However, the overproduction of MPO-derived oxidants has drawn attention to its detrimental role, especially in diseases characterized by acute or chronic inflammation. Broadly speaking, MPO and its derived oxidants are involved in the pathological processes of diseases mainly through the oxidation of biomolecules, which promotes inflammation and oxidative stress. Meanwhile, some researchers found that MPO deficiency or using MPO inhibitors could attenuate inflammation and tissue injuries. Taken together, MPO might be a promising target for both prognostic and therapeutic interventions. Therefore, understanding the role of MPO in the progress of various diseases is of great value. This review provides a comprehensive analysis of the diverse roles of MPO in the progression of several diseases, including cardiovascular diseases (CVDs), neurodegenerative diseases, cancers, renal diseases, and lung diseases (including COVID-19). This information serves as a valuable reference for subsequent mechanistic research and drug development. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma (HNSCC) is a very heterogeneous cancer with a poor overall response to therapy. One of the reasons for this therapy resistance could be cancer stem cells (CSCs), a small population of cancer cells with self-renewal and tumor-initiating abilities. Tumor cell heterogeneity represents hurdles for therapeutic elimination of CSCs. Different signaling pathway activations, such as Wnt, Notch, and Sonic-Hedgehog (SHh) pathways, lead to the expression of several cancer stem factors that enable the maintenance of CSC features. Identification and isolation of CSCs are based either on markers (CD133, CD44, and aldehyde dehydrogenase (ALDH)), side populations, or their sphere-forming ability. A key challenge in cancer therapy targeting CSCs is overcoming chemotherapy and radiotherapy resistance. However, in novel therapies, various approaches are being employed to address this hurdle such as targeting cell surface markers, other stem cell markers, and different signaling or metabolic pathways, but also, introducing checkpoint inhibitors and natural compounds into the therapy can be beneficial. [ABSTRACT FROM AUTHOR]

The role of desmoglein-3 (DSG3) in oncogenesis is unclear. This study aimed to uncover molecular mechanisms through comparative transcriptome analysis in oral cancer cells, defining potential key genes and associated biological processes related to DSG3 expression. Four mRNA libraries of oral squamous carcinoma H413 cell lines were sequenced, and 599 candidate genes exhibited differential expression between DSG3-overexpressing and matched control lines, with 12 genes highly significantly differentially expressed, including 9 upregulated and 3 downregulated. Genes with known implications in cancer, such as MMP-13, KRT84, OLFM4, GJA1, AMOT and ADAMTS1, were strongly linked to DSG3 overexpression. Gene ontology analysis indicated that the DSG3-associated candidate gene products participate in crucial cellular processes such as junction assembly, focal adhesion, extracellular matrix formation, intermediate filament organisation and keratinocyte differentiation. Validation of RNA-Seq was performed through RT-qPCR, Western blotting and immunofluorescence analyses. Furthermore, using transmission electron microscopy, we meticulously examined desmosome morphology and revealed a slightly immature desmosome structure in DSG3-overexpressing cells compared to controls. No changes in desmosome frequency and diameter were observed between the two conditions. This study underscores intricate and multifaceted alterations associated with DSG3 in oral squamous carcinoma cells, implying a potential oncogenic role of this gene in biological processes that enable cell communication, motility and survival. [ABSTRACT FROM AUTHOR]

Odontomas are considered hamartomatous lesions and are one of the two most common odontogenic tumors of the jaw. Odontomas are classified as compound or complex. Recently, ameloblastic fibro-odontoma (AFO) and ameloblastic fibro-dentinoma were reclassified as developing odontomas. Though clinically odontomas are usually asymptomatic, they have adverse effects on adjacent teeth such as tooth impaction, delayed eruption, displacement of teeth, over-retention of teeth, and can give rise to odontogenic cysts within the jaw. We sought to evaluate the clinicoradiopathologic presentations of odontomas by collecting and analyzing the clinical, radiographic, and pathologic data of odontomas diagnosed in our institution from 2013 to 2022. Over this 10-year period, there were 242 patients with a histopathological and/or radiographic diagnosis of odontoma. There was no gender predilection and ages ranged from 3 to 101 years (median, 14 years). The second decade of life was the most prevalent (57.4%). There was no jaw predilection; however, the anterior jaw was the most common location. Ninety-four (38.8%) cases presented with clinical findings. The most common finding was tooth impaction (n = 83). Nine (3.7%) cases were histopathologically confirmed to be associated with other lesions such as dentigerous cysts (n = 8) and nasopalatine duct cyst (n = 1). The median age (25 years) of patients diagnosed with odontomas associated with cysts was older than patients with odontomas (14 years) without associated cysts. Compound odontomas were the most common type of odontoma compared to complex and AFOs with 71.4%, 26.6%, and 2%, respectively. The majority of compound odontomas involved the anterior jaw (69.3%) and mandible (54.9%) while the majority of complex odontomas involved the posterior jaw (59.6%) and maxilla (54.7%). The four AFOs were in the posterior jaw and 75% involved the maxilla. The median age (12 years) of patients diagnosed with AFO was the youngest compared to patients diagnosed with compound (13 years) and complex (16 years). In conclusion, we analyzed the clinical, radiographic, and pathologic features of 242 new cases of odontomas. Our study reaffirms that odontomas frequently affect the pediatric population and can disrupt their dentition. Based on the result of this study, our clinical recommendation to prevent problems to adjacent teeth from odontomas is for dentists to be apt in the diagnose of odontomas to ensure that they are surgically removed in a timely manner. [ABSTRACT FROM AUTHOR]

Oral lichen planus (OLP) is classified as a potentially malignant disorder. Systematic reviews collating longitudinal observation studies provide evidence of the rate or proportion of malignant transformation. We conducted an umbrella study of published systematic reviews. An extensive English-language study search was carried out in several databases to identify relevant articles, providing systematic reviews on the malignant transformation of OLP. Data from eight systematic reviews published between 2014 and 2023 are presented. The reported proportions of malignant transformation ranged from 1.1% to 1.4%. A meta-analysis based on the 10 highest-quality studies yielded a higher proportion of malignant transformation (2.28%). We list some limitations found in several of these systematic reviews. Some studies reported an increased risk of malignancy in OLP lesions, demonstrating epithelial dysplasia. In view of the consistent evidence of the risk of oral malignancy, OLP patients should be monitored carefully to detect early cancer development. [ABSTRACT FROM AUTHOR]

Background: The use of human dentin matrix could serve as an alternative to autologous, allogenic, and xenogeneic bone grafts due to its osteoinductive characteristics. The limitations of its use is tooth availability and that it is often necessary to mix it with a biomaterial. Aim: The aim of this study was to analyze a mix of two different graft materials with different reabsorption ranges when the dentin graft material was not sufficient for full socket preservation. Methods: Seven socket preservation surgeries were carried out employing a mixed graft material containing 50% dentin and 50% xenograft. After four months of recovery, the implants were positioned. At the time of the prosthesis placement and implant surgery, bone samples were collected. Results: The histologic analysis revealed no inflammatory or infective reaction against the seven biopsies. The histomorphometric graft analysis revealed an amount of New Bone of 29.03 ± 6.57% after 4 months and 34.11 ± 5.02% after 8 months. Conclusions: The two graft materials had a different volume reabsorption rate: 71% after 4 months and 90% after 8 months for dentin, and 6% after 4 months and 26% after 8 months for the xenograft. The space created by the dentin reabsorption increased the quantity of new bone. [ABSTRACT FROM AUTHOR]

OP-145 and SAAP-148, two 24-mer antimicrobial peptides derived from human cathelicidin LL-37, exhibit killing efficacy against both Gram-positive and Gram-negative bacteria at comparable peptide concentrations. However, when it comes to the killing activity against Escherichia coli, the extent of membrane permeabilization does not align with the observed bactericidal activity. This is the case in living bacteria as well as in model membranes mimicking the E. coli cytoplasmic membrane (CM). In order to understand the killing activity of both peptides on a molecular basis, here we studied their mode of action, employing a combination of microbiological and biophysical techniques including differential scanning calorimetry (DSC), zeta potential measurements, and spectroscopic analyses. Various membrane dyes were utilized to monitor the impact of the peptides on bacterial and model membranes. Our findings unveiled distinct binding patterns of the peptides to the bacterial surface and differential permeabilization of the E. coli CM, depending on the smooth or rough/deep-rough lipopolysaccharide (LPS) phenotypes of E. coli strains. Interestingly, the antimicrobial activity and membrane depolarization were not significantly different in the different LPS phenotypes investigated, suggesting a general mechanism that is independent of LPS. Although the peptides exhibited limited permeabilization of E. coli membranes, DSC studies conducted on a mixture of synthetic phosphatidylglycerol/phosphatidylethanolamine/cardiolipin, which mimics the CM of Gram-negative bacteria, clearly demonstrated disruption of lipid chain packing. From these experiments, we conclude that depolarization of the CM and alterations in lipid packing plays a crucial role in the peptides' bactericidal activity. [ABSTRACT FROM AUTHOR]

Simple Summary: We are going to highlight new prognostic and predictive factors, CD44, PDL1, and ATG7, in surgical samples from patients with laryngeal squamous cell carcinoma (LSCC). Immunohistochemical analysis with primary antibodies anti-CD44, PD-L1 and ATG7 was performed using the tissue microarray (TMA) technique. Considering follow-up data, the 5-year disease-free survival (DFS) was 85.71% and 36% for CD44-negative and -positive tumors. The 5-year DFS was 60% and 33.33% for negative and positive PDL1 tumors, respectively. At the follow-up, 5-year DFS was 58.06% and 37.50% for negative and positive ATG7 tumors. We focus on the new prognostic and predictive factors CD44, PDL1, and ATG7 in our study of surgical samples of patients with laryngeal squamous cell carcinoma (LSCC) using tissue microarray (TMA). Thirty-nine previously untreated patients affected by laryngeal carcinoma who then underwent surgical treatment were considered in this retrospective study. All surgical specimens were sampled, embedded in paraffin blocks, and stained with hematoxylin and eosin. A representative sample of the tumor was chosen and transferred into a new block of paraffin, the recipient block, to perform immunohistochemical analysis with the primary antibodies anti-CD44, PD-L1, and ATG7. At follow-up, 5-year disease-free survival (DFS) for negative and positive tumors was determined as 85.71% and 36% for CD44, 60% and 33.33% for PDL1, and 58.06% and 37.50% for ATG7, respectively. Multivariate analysis revealed that CD44 expression is an independent predictive factor of low-grade tumors (p = 0.008), lymph node metastasis at the time of diagnosis, and AGT7 negativity. Thus, CD44 expression is a potential marker for more aggressive forms of laryngeal cancer. [ABSTRACT FROM AUTHOR]

Lactoferrin is an iron-binding glycoprotein present in most human exocrine fluids, particularly breast milk. Lactoferrin is also released from neutrophil granules, and its concentration increases rapidly at the site of inflammation. Immune cells of both the innate and the adaptive immune system express receptors for lactoferrin to modulate their functions in response to it. On the basis of these interactions, lactoferrin plays many roles in host defense, ranging from augmenting or calming inflammatory pathways to direct killing of pathogens. Complex biological activities of lactoferrin are determined by its ability to sequester iron and by its highly basic N-terminus, via which lactoferrin binds to a plethora of negatively charged surfaces of microorganisms and viruses, as well as to mammalian cells, both normal and cancerous. Proteolytic cleavage of lactoferrin in the digestive tract generates smaller peptides, such as N-terminally derived lactoferricin. Lactoferricin shares some of the properties of lactoferrin, but also exhibits unique characteristics and functions. In this review, we discuss the structure, functions, and potential therapeutic uses of lactoferrin, lactoferricin, and other lactoferrin-derived bioactive peptides in treating various infections and inflammatory conditions. Furthermore, we summarize clinical trials examining the effect of lactoferrin supplementation in disease treatment, with a special focus on its potential use in treating COVID-19. [ABSTRACT FROM AUTHOR]

There are many cysts and tumors which might occur in the mandibular and maxillary bones. Their origin can be either odontogenic or non-odontogenic. One of the most common odontogenic cysts is the odontogenic keratocyst (OKC). Its nomenclature and classification have changed many times over years, from a tumor to, finally, a cyst. Nowadays, its treatment has not greatly changed, however, it is related to a potential recurrence rate more than any other cyst of odontogenic origins. OKC size, localization, and possible cortical expansion towards adjacent soft tissues might influence the scope of treatment and possible reoccurrence in time. Each case is quite individual, and after removal of the pathology in some cases there can be a necessity for either bone grafting or any other reconstruction method to restore proper bone continuity. The size and the placement of OKC might influence pathological fracture occurrence or inappropriate healing if the bone cavity after cyst removal is not properly treated. A good healing potential can be achieved with xenograft bone substitutes or allograft fresh–frozen bones. On rare occasions, a titanium plate is used to ensure mandibular stability. In the following case report, an atypical case of a large OKC treated with fresh–frozen bone grafts, supported with collagen barrier material in the anterior mandible with buccal cortical expansion, will be presented. [ABSTRACT FROM AUTHOR]

Introduction: Salivary gland carcinomas (SGC) are histologically diverse cancers and next-generation sequencing (NGS) to identify key molecular targets is an important aspect in the management of advanced cases. Methods: DNA was extracted from paraffin embedded tissues of advanced SGC and comprehensive genomic profiling (CGP) was carried out to evaluate for base substitutions, short insertions, deletions, copy number changes, gene fusions and rearrangements. Tumor mutation burden (TMB) was calculated on approximately 1.25 Mb. Some 324 genes in the FoundationOne CDX panel were analyzed. Results: Mucoepidermoid carcinoma (MECa) mutations were assessed. CDKN2A and CDKN2B GA were common in mucoepidermoid carcinoma (MECa) (52.5 and 30.5%). PIK3CA was also common in MECa (16.9%). ERBB2 amplification/short variants (amp/SV) were found in MECa (5.9/0%). HRAS GA was common in MECa (14.4%) as well. Other targets, including BAP1, PTEN, and KRAS, were noted but had a low incidence. In terms of immunotherapy (IO)-predictive markers, TMB > 10 was more common in MECa (16.9%). PDL1 high was also seen in MECa (4.20%). Conclusion: SGC are rare tumors with no FDA-approved treatment options. This large dataset reveals many opportunities for IO and targeted therapy contributing to the continuously increased precision in the selection of treatment for these patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer cells commonly escape cell death and proliferate endlessly. We review the molecular mechanisms that are fundamental to this process and suggest that these changes also lead to instability in the genetic make-up (genes and chromosomes) of putative cancer cells. In this way, cells in the very early stages of cancer development acquire unlimited growth potential and also develop cellular diversity, which may facilitate more aggressive cell behaviour and the development of overt cancer. These observations have important clinical implications. We highlight a recent sensitive technique to detect chromosome instability in cells that are shed into the saliva, which can be used for the detection of the early stages of cancer of the mouth. In addition, we discuss new drug developments that are designed to target chromosome instability and, therefore, eliminate potentially dangerous cells before cancer development. An escape from cellular senescence through the development of unlimited growth potential is one of the hallmarks of cancer, which is thought to be an early event in carcinogenesis. In this review, we propose that the molecular effectors of senescence, particularly the inactivation of TP53 and CDKN2A, together with telomere attrition and telomerase activation, all lead to aneuploidy in the keratinocytes from oral potentially malignant disorders (OPMD). Premalignant keratinocytes, therefore, not only become immortal but also develop genotypic and phenotypic cellular diversity. As a result of these changes, certain clonal cell populations likely gain the capacity to invade the underlying connective tissue. We review the clinical implications of these changes and highlight a new PCR-based assay to identify aneuploid cell in fluids such as saliva, a technique that is extremely sensitive and could facilitate the regular monitoring of OPMD without the need for surgical biopsies and may avoid potential biopsy sampling errors. We also draw attention to recent studies designed to eliminate aneuploid tumour cell populations that, potentially, is a new therapeutic approach to prevent malignant transformations in OPMD. [ABSTRACT FROM AUTHOR]

The occurrence and manifestation of each ameloblastic fibro-odontoma (AFO) is quite rare and uncommon. Mentioned odontogenic tumor classification had changed over the years; however, the treatment possibilities for this lesion remain the same. In most cases surgical enucleation is sufficient enough; however, bigger lesions might require bone curettage with sometimes performed bony ostectomy, which is a quite sufficient and effective method of treatment. In the presented case report, a panoramic radiological evaluation indicated an impacted molar tooth surrounded with mixed radiolucent/radiopaque areas. The 10-year-old Caucasian girl was scheduled for an incisional biopsy. The bone cavity in the mandible after tumor removal might be left for spontaneous healing or grafting techniques, depending on the shape and size of the defect. In the presented case report, the usage of PRF/iPRF in the mandibular bone cavity, and healing improved the overall final result. [ABSTRACT FROM AUTHOR]

Simple Summary: The study was the first to screen seven genes and identify the set of genes using twelve machine learning algorithms that predict the progression from oral leukoplakia to oral squamous cell carcinoma. We verified these genes by RT-qPCR experiments and speculated on the possible molecular mechanisms through the results. These genes could be used as biomarkers for early diagnosis and predicting patients with a high risk of malignant transformation. This will aid in early intervention, improve the patient prognosis, and reduce the incidences of oral squamous cell carcinoma. The aim of the study is to identify key genes during the progression from oral leukoplakia (OL) to oral squamous cell carcinoma (OSCC) and predict effective diagnoses. Weighted gene co-expression network analysis (WGCNA) and differential expression analysis were performed to identify seven genes associated with the progression from OL to OSCC. Twelve machine learning algorithms including k-nearest neighbor (KNN), neural network (NNet), and extreme gradient boosting (XGBoost) were used to construct multi-gene models, which revealed that each model had good diagnostic efficacy. The functional mechanism or the pathways associated with these genes were evaluated using enrichment analysis, subtype clustering, and immune infiltration analysis. The enrichment analysis revealed that the genes enriched were associated with the cell cycle, cell division, and intracellular energy metabolism. The immunoassay results revealed that the genes primarily affected the infiltration of proliferating T cells and macrophage polarization. Finally, a nomogram and Kaplan–Meier survival analysis were used to predict the prognostic efficacy of key genes in OSCC patients. The results showed that genes could predict the prognosis of the patients, and patients in the high-risk group had a poor prognosis. Our study identified that the seven key genes, including DHX9, BCL2L12, RAD51, MELK, CDC6, ANLN, and KIF4A, were associated with the progression from OL to OSCC. These genes had good diagnostic efficacy and could be used as potential biomarkers for the prognosis of OSCC patients. [ABSTRACT FROM AUTHOR]

Oral lichen planus (OLP) is a common chronic inflammatory disease of unknown etiology and likely autoimmune nature that is currently considered an oral potentially malignant disorder, implying that patients suffering from this process are at risk of developing oral cancer in their lifetime. The molecular alterations that develop in OLP and that make the affected oral epithelium predisposed to malignancy are unknown, although, as in other autoimmune diseases (ulcerative colitis, primary biliary cirrhosis, etc.), they may be linked to oncogenesis-promoting effects mediated by the inflammatory infiltrate. So far there is no in-depth knowledge on how these hallmarks of cancer are established in the cells of the oral epithelium affected by OLP. In this scoping review of systematic reviews and meta-analyses the state of evidence based knowledge in this field is presented, to point out gaps of evidence and to indicate future lines of research. MEDLINE, Embase, Cochrane Library and Dare were searched for secondary-level studies published before October 2022. The results identified 20 systematic reviews and meta-analyses critically appraising the hallmarks tumor-promoting inflammation (n = 17, 85%), sustaining proliferative signaling (n = 2, 10%), and evading growth suppressors (n = 1, 5%). No evidence was found for the other hallmarks of cancer in OLP. In conclusion, OLP malignization hypothetically derives from the aggressions of the inflammatory infiltrate and a particular type of epithelial response based on increased epithelial proliferation, evasion of growth-suppressive signals and lack of apoptosis. Future evidence-based research is required to support this hypothesis. [ABSTRACT FROM AUTHOR]

Human cytomegalovirus (HCMV) DNA and proteins are often detected in malignant tumors, warranting studies of the role that HCMV plays in carcinogenesis and tumor progression. HCMV proteins were shown to regulate the key processes involved in tumorigenesis. While HCMV as an oncogenic factor just came into focus, its ability to promote tumor progression is generally recognized. The review discusses the viral factors and cell molecular pathways that affect the resistance of cancer cells to therapy. CMV inhibits apoptosis of tumor cells, that not only promotes tumor progression, but also reduces the sensitivity of cells to antitumor therapy. Autophagy was found to facilitate either cell survival or cell death in different tumor cells. In leukemia cells, HCMV induces a "protective" autophagy that suppresses apoptosis. Viral factors that mediate drug resistance and their interactions with key cell death pathways are necessary to further investigate in order to develop agents that can restore the tumor sensitivity to anticancer drugs. [ABSTRACT FROM AUTHOR]

Methotrexate (MTX) administration is the gold standard treatment for rheumatoid arthritis (RA), but its effects are limited to preventing the progression of the disease. Therefore, effective regenerative therapies for damaged tissues are still to be developed. In this regard, MTX complexes of general molecular formula M(MTX)·xH2O, where M = Sr, Zn, or Mg, were synthesized and physicochemically characterized by TGA, XRD, NMR, ATR–FTIR, and EDAX spectroscopies. Characterization results demonstrated the coordination between the different cations and MTX via two monodentate bonds with the carboxylate groups of MTX. Cation complexation provided MTX with new bioactive properties such as increasing the deposition of glycosaminoglycans (GAGs) and alternative anti-inflammatory capacities, without compromising the immunosuppressant properties of MTX on macrophages. Lastly, these new complexes were loaded into spray-dried chitosan microparticles as a proof of concept that they can be encapsulated and further delivered in situ in RA-affected joints, envisioning them as a suitable alternative to oral MTX therapy. [ABSTRACT FROM AUTHOR]

(1) Background: The aim of this study was to compare the histopathological features of syndromic and non-syndromic odontogenic keratocysts (OKs) using conventional and Confocal Laser Scanning Microscopy (CLSM) with their biological behaviour. (2) Methods: Data from the medical records of 113 patients with histological diagnosis of (single and/or multiple) OKs were collected. Globally, 213 OKs (120 syndromic and 93 sporadic) were retrieved, and their histological slides were re-evaluated with conventional H&E staining and with autofluorescence on the same slides using CLSM (Nikon Eclipse E600 microscope). (3) Results: Syndromic OKs showed more satellite cysts than sporadic cases, as well as a basophilic layer in the basement membrane, which was absent in sporadic OKs; both were highlighted with CLSM. The basement membrane in syndromic OKs appeared amorphous and fragile, thus possibly being responsible for the epithelial detachment and collapse, with scalloped features. Furthermore, the basal epithelial layers in such cases also showed increased cellularity and proliferative activity. All these histological features may possibly justify their higher tendency to recur. (4) Conclusions: CLSM is useful advanced technology that could help to quickly and easily discriminate between syndromic and non-syndromic OKs and to more accurately predict their biological behaviour in order to set fitter clinico-radiological follow-ups for individual patients. [ABSTRACT FROM AUTHOR]

Oral potentially malignant disorders (OPMDs) are a group of diseases involving the oral mucosa and that have a risk of carcinogenesis. The microenvironment is closely related to carcinogenesis and cancer progression by regulating the immune response, cell metabolic activities, and mechanical characteristics. Meanwhile, there are extensive interactions between the microenvironments that remodel and provide favorable conditions for cancer initiation. However, the changes, exact roles, and interactions of microenvironments during the carcinogenesis of OPMDs have not been fully elucidated. Here, we present an updated landscape of the microenvironments in OPMDs, emphasizing the changes in the immune microenvironment, metabolic microenvironment, mechanical microenvironment, and neural microenvironment during carcinogenesis and their carcinogenic mechanisms. We then propose an immuno–metabolic–mechanical–neural interaction network to describe their close relationships. Lastly, we summarize the therapeutic strategies for targeting microenvironments, and provide an outlook on future research directions and clinical applications. This review depicts a vivid microenvironment landscape and sheds light on new strategies to prevent the carcinogenesis of OPMDs. [ABSTRACT FROM AUTHOR]

Pleomorphic adenoma (PA) is a localized tumor that presents pleomorphic or mixed characteristics of epithelial origin and is interwoven with mucoid tissue, myxoid tissue, and chondroid masses. The literature reported that PA most often occurs in adults aged 30–60 years and is a female predilection; the exact etiology remains unclear. Epithelial–mesenchymal transition (EMT) is the transdifferentiation of stationary epithelial cells primarily activated by a core set of transcription factors (EMT-TFs) involved in DNA repair and offers advantages under various stress conditions. Data have suggested that EMTs represent the basic principle of tissue heterogeneity in PAs, demonstrating the potential of adult epithelial cells to transdifferentiate into mesenchymal cells. It has also been reported that multiple TFs, such as TWIST and SLUG, are involved in EMT in PA and that SLUG could play an essential role in the transition from myoepithelial to mesenchymal cells. Given this background, this review aims to summarize and clarify the involvement of EMT in the development of PA, chondrocyte differentiation, and malignant transformation to contribute to the fundamental elucidation of the mechanisms underlying EMT. [ABSTRACT FROM AUTHOR]

Gyrovirus galga 1 (GyVg1, previously recognized as avian gyrovirus 2), which was first reported in chicken in 2011, is a new member of the genus Gyrovirus. The presence of GyVg1 has also been confirmed in different regions of Europe, South America, Africa, and Asia, indicating its global distribution. However, because there are no reports of examining the distribution of GyVg1 in animals in Japan, the epidemiology of this virus is unknown. In this study, we attempted to retrospectively detect GyVg1 in cryopreserved chicken materials derived from different two commercial broiler flocks in 1997. The GyVg1 genome was detected in organ materials derived from both flocks by PCR. GyVg1 detected in both flocks was classified into four genetic groups by analyzing the nucleotide sequences of the detected PCR products. These results suggest that diverse GyVg1 strains were present in commercial chicken flocks as early as 1997 in Japan. [ABSTRACT FROM AUTHOR]

Desquamative gingivitis (DG) is a clinical term that describes erythema, desquamation and erosions of the gingiva, of various etiologies. Although the clinical aspect is not specific for a certain disease, an accurate diagnosis of the underlying disorder is necessary because the disease course, prognosis and treatment vary according to the cause. DG may inflict significant oral discomfort, which is why patients typically present to the dentist for a first consultation, rendering it important for these specialists to be informed about this condition. Our paper aims to review the ethiopatogenesis and diagnostic approach of DG, focusing on the most common underlying disorders (autoimmune bullous dermatoses and lichen planus) and on the management of these patients. Potential etiological agents leading to an inflammatory immune response in the oral mucosa and DG appearance include genetic predisposition, metabolic, neuropsychiatric, infectious factors, medication, dental materials, graft-versus-host reaction and autoimmunity. A thorough anamnesis, a careful clinical examination, paraclinical explorations including histopathological exam and direct immunofluorescence are necessary to formulate an appropriate diagnosis. Proper and prompt management of these patients lead to a better prognosis and improved quality of life, and must include management in the dental office with sanitizing the oral cavity, instructing the patient for rigorous oral hygiene, periodic follow-up for bacterial plaque detection and removal, as well as topical and systemic therapy depending on the underlying disorder, based on treatment algorithms. A multidisciplinary approach for the diagnosis and follow-up of DG in the context of pemphigus vulgaris, bullous pemphigoid, cicatricial pemhigoid or lichen planus is necessary, including consultations with dermatologists, oral medicine specialists and dentists. [ABSTRACT FROM AUTHOR]

The diagnosis and treatment of maxillofacial cystic lesions requires careful evaluation and correlation of the clinical presentation and radiological studies. The Pindborg tumor, also known as the calcifying epithelial odontogenic tumor, is a locally invasive benign neoplasm, with only around 300 cases being published to date. This study presents a new case of this already uncommon neoplasm, not associated with an impacted tooth, and describes the clinicopathological features of this rare entity, along with a review of other reported cases. Despite surgery having been recognized as the treatment of choice for the Pindborg tumor, no firm consensus exists concerning the extension of surgical resection. [ABSTRACT FROM AUTHOR]

A review of the carcinogenic effects of ochratoxin A (OTA) on various tissues and internal organs in laboratory and farm animals is made. Suggestions are made regarding how to recognize and differentiate the common spontaneous neoplastic changes characteristic for advanced age and the characteristic neoplasia in different tissues and organs in laboratory animals/poultry exposed to OTA. The synergistic effects of OTA together with its natural combination of penicillic acid are also investigated regarding possible carcinogenic effects. The malignancy and the target location of OTA-induced neoplasia is studied. The sex-differences of such neoplasia are investigated in the available literature. The time of appearance of the first neoplasia is investigated in long-term carcinogenic studies with OTA-treated animals. The possibility of target feed additives or herbs to counteract the toxic and carcinogenic effects of OTA is studied in the available literature. Some effective manners of prophylaxis and/or prevention against OTA contamination of feedstuffs/foods or animal production are suggested. The suitability of various laboratory animals to serve as experimental model for humans with regard to OTA-induced tumorigenesis is investigated. [ABSTRACT FROM AUTHOR]

Syphilis is an infectious disease caused by Treponema pallidum. Syphilis can present with an array of oral manifestations at different stages of disease progression. This article reports on four cases of syphilis with oral manifestations diagnosed by oral health professionals. Case 1: 18-year-old female presented with multiple ulcerations and patches involving the hard palate, uvula, retromolar area, and papillary nodules on the tongue. Case 2: 25-year-old male presented with a solitary, exophytic lesion on the anterior tongue. Case 3: 17-year-old female presented with multiple pigmented macules on the palms of hands and soles of feet, as well as multiple exophytic, sessile, soft tissue masses throughout the oral cavity. Case 4: 14-year-old female presented with a solitary, exophytic, verrucous lesion in the incisive papilla area, as well as multiple, coalescing patches involving the soft palate, uvula, and tonsillar areas. All patients were managed by biopsy and serological investigations. Treatment of syphilis was performed at infectious disease clinics with 2.4 million units (MUs) benzathine benzylpenicillin intramuscular (IM) weekly. Oral health professionals need to have knowledge of the oral manifestations of syphilis to ensure that patients are accurately identified and appropriately treated. [ABSTRACT FROM AUTHOR]

Mucoepidermoid carcinoma (MEC) is often seen in salivary glands and can harbor MAML2 translocations (MAML2+). The translocation status has diagnostic utility as an objective confirmation of the MEC diagnosis, for example, when distinction from the more aggressive adenosquamous carcinoma (ASC) is not straightforward. To assess the diagnostic relevance of MAML2, we examined our 5-year experience in prospective testing of 8106 solid tumors using RNA-seq panel testing in combinations with a two-round Delphi-based scenario survey. The prevalence of MAML2+ across all tumors was 0.28% (n = 23/8106) and the majority of MAML2+ cases were found in head and neck tumors (78.3%), where the overall prevalence was 5.9% (n = 18/307). The sensitivity of MAML2 for MEC was 60% and most cases (80%) were submitted for diagnostic confirmation; in 24% of cases, the MAML2 results changed the working diagnosis. An independent survey of 15 experts showed relative importance indexes of 0.8 and 0.65 for "confirmatory MAML2 testing" in suspected MEC and ASC, respectively. Real-world evidence confirmed that the added value of MAML2 is a composite of an imperfect confirmation test for MEC and a highly specific exclusion tool for the diagnosis of ASC. Real-world evidence can help move a rare molecular-genetic biomarker from an emerging tool to the clinic. [ABSTRACT FROM AUTHOR]

Non-plaque induced diffuse gingival overgrowth represents a broad class of conditions caused by several etiological factors. The aim of this review is to highlight the most recent updates and classifications of all the existent gingival overgrowths. In addition, we highlighted the diagnostic pathway that should be employed in patients affected by gingival overgrowth. Gingival overgrowth can be related to syndromic diseases including a wide spectrum of genetic and chromosomal alterations. However, thanks to scientific sharing and the availability of genetic panels it is possible to obtain an accurate phenotypic identification of well-known syndromes and also to identify new ones. This narrative review shows that through rigid, strict diagnostic protocols, the work of the clinician is greatly facilitated, despite the wide variety of pathologies considered. In conclusion, the exchange of specialists' competencies and the multidisciplinary management of these patients, are crucial to reach diagnosis and the correct clinical-therapeutic management. [ABSTRACT FROM AUTHOR]

Simple Summary: Incisional tissue biopsy is highly invasive, but it remains the current practice for oral cancer diagnosis through histopathological interpretation. To reduce biopsy invasiveness without compromising diagnosis, we pioneered a multigene RT-qPCR method for cancer detection using only a tiny 1 mm3 minimally invasive biopsy. Here we presented international multicohort validation of our second-generation method which involved new genes from matrix/stroma and immune regulations enabling sensitive, quantitative and precise oral cancer detection in otherwise ambiguous oral lesions. Background: Heterogeneity in oral potentially malignant disorder (OPMD) poses a problem for accurate prognosis that impacts on treatment strategy and patient outcome. A holistic assessment based on gene expression signatures from both the tumour cells and their microenvironment is necessary to provide a more precise prognostic assessment than just tumour cell signatures alone. Methods: We reformulated our previously established multigene qPCR test, quantitative Malignancy Index Diagnostic System (qMIDS) with new genes involved in matrix/stroma and immune modulation of the tumour microenvironment. An algorithm calculates and converts a panel of 16 gene mRNA expression levels into a qMIDS index to quantify risk of malignancy for each sample. Results: The new qMIDSV2 assay was validated in a UK oral squamous cell carcinoma (OSCC) cohort (n = 282) of margin and tumour core samples demonstrating significantly better diagnostic performance (AUC = 0.945) compared to previous qMIDSV1 (AUC = 0.759). Performance of qMIDSV2 were independently validated in Chinese (n = 35; AUC = 0.928) and Indian (n = 95; AUC = 0.932) OSCC cohorts. Further, 5-year retrospective analysis on an Indian dysplastic lesion cohort (n = 30) showed that qMIDSV2 was able to significantly differentiate between lesions without transformation and those with malignant transformation. Conclusions: This study validated a novel multi-gene qPCR test on a total of 535 tissue specimens from UK, China and India, demonstrating a rapid minimally invasive method that has a potential application for dysplasia risk stratification. Further study is required to establish if qMIDSV2 could be used to improve OPMD patient management, guide treatment strategy and reduce oral cancer burden. [ABSTRACT FROM AUTHOR]

Penicillium polonicum K. M. Zaleski, which is common on foodstuffs in Balkan regions that are notable for their history of endemic nephropathy, has been shown experimentally to cause a striking histopathological renal change in rats that are given feed contaminated by this fungus. The nephrotoxic agent(s) are only partially characterized. The principal change seen in the cortico-medullary region is karyocytomegaly, but apoptosis, identified with the ApopTag® methodology, is the first response to a dietary extract of P. polonicum-molded wheat after a few days of exposure. Chromatin debris migrates along the nephrons into the medulla, but whether the damaged epithelial fate is via autophagy is unclear. In intermittent exposure experiments, renal apoptosis was resolved with the cessation of exposure and was restored with renewed exposure. Apoptosis became less evident after 3 months of chronic exposure. In contrast, a relatively high dose of dietary ochratoxin A, a potent nephrocarcinogen in male rats after many months of dietary exposure, gave no evidence of apoptosis in asymptomatic weanlings over a few days of dietary exposure. This was attributed to a masking effect by concomitant marked histological disruption in renal tissue. However, in young adults, renal apoptosis was a primary outcome of dietary exposure to either the P. polonicum extract or to ochratoxin A, but the histopathological response to the former was less distorted. The apparent conflicted use in the literature of P. polonicum as a descriptor is highlighted. [ABSTRACT FROM AUTHOR]

In this study, we aimed to investigate the bone regeneration efficiency of two-layer porcine-derived bone scaffolds composed of cancellous and cortical bones in a rabbit calvarial defect model. Four circular calvaria defects were formed on cranium of rabbit and were filled with block bone scaffolds of each group: cortical bone block (Cortical group), cancellous bone block (Cancellous group), and two-layer bone block (2layer group). After 8 weeks, new bones were primarily observed in cancellous parts of the Cancellous and 2layer groups, while the Cortical group exhibited few new bones. In the results of new bone volume and area analyses, the Cancellous group showed the highest value, followed by the 2layer group, and were significantly higher than the Cortical group. Within the limitations of this study, the cancellous and two-layer porcine-derived bone scaffolds showed satisfactory bone regeneration efficiency; further studies on regulating the ratio of cortical and cancellous bones in two-layer bones are needed. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a very poor prognosis. Its treatment is hindered by a lack of new therapeutic alternatives and the existence of the blood–brain barrier (BBB), which restricts the access of drugs commonly used in ALS, such as riluzole, to the brain. To overcome these limitations and increase brain targeting, riluzole-loaded nanostructured lipid carriers (NLC) were prepared and functionalized with lactoferrin (Lf), facilitating transport across the BBB by interacting with Lf receptors expressed in the brain endothelium. NLC were characterized with respect to their physicochemical properties (size, zeta potential, polydispersity index) as well as their stability, encapsulation efficiency, morphology, in vitro release profile, and biocompatibility. Moreover, crystallinity and melting behavior were assessed by DSC and PXRD. Nanoparticles exhibited initial mean diameters between 180 and 220 nm and a polydispersity index below 0.3, indicating a narrow size distribution. NLC remained stable over at least 3 months. Riluzole encapsulation efficiency was very high, around 94–98%. FTIR and protein quantification studies confirmed the conjugation of Lf on the surface of the nanocarriers, with TEM images showing that the functionalized NLC presented a smooth surface and uniform spherical shape. An MTT assay revealed that the nanocarriers developed in this study did not cause a substantial reduction in the viability of NSC-34 and hCMEC/D3 cells at a riluzole concentration up to 10 μM, being therefore biocompatible. The results suggest that Lf-functionalized NLC are a suitable and promising delivery system to target riluzole to the brain. [ABSTRACT FROM AUTHOR]

Biomedical imaging technologies offer identification of several anatomic and molecular features of disease pathogenesis. Molecular imaging techniques to assess cellular processes in vivo have been useful in advancing our understanding of several vascular inflammatory diseases. For the non-invasive molecular imaging of vascular inflammation, nuclear medicine constitutes one of the best imaging modalities, thanks to its high sensitivity for the detection of probes in tissues. 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG) is currently the most widely used radiopharmaceutical for molecular imaging of vascular inflammatory diseases such as atherosclerosis and large-vessel vasculitis. The combination of [18F]FDG and positron emission tomography (PET) imaging has become a powerful tool to identify and monitor non-invasively inflammatory activities over time but suffers from several limitations including a lack of specificity and avid background in different localizations. The use of novel radiotracers may help to better understand the underlying pathophysiological processes and overcome some limitations of [18F]FDG PET for the imaging of vascular inflammation. This review examines how [18F]FDG PET has given us deeper insight into the role of inflammation in different vascular pathologies progression and discusses perspectives for alternative radiopharmaceuticals that could provide a more specific and simple identification of pathologies where vascular inflammation is implicated. Use of these novel PET tracers could lead to a better understanding of underlying disease mechanisms and help inform the identification and stratification of patients for newly emerging immune-modulatory therapies. Future research is needed to realize the true clinical translational value of PET imaging in vascular inflammatory diseases. [ABSTRACT FROM AUTHOR]

Several recent studies have shown that both strands of certain miRNAs derived from miRNA duplexes are involved in cancer pathogenesis. Our own recent studies revealed that both strands of the miR-150 duplex act as tumor-suppressive miRNAs in lung adenocarcinoma (LUAD) through the targeting of several oncogenes. The aim of the study here was to further investigate the tumor-suppressive roles of miR-150-3p (the passenger strand) in lung squamous cell carcinoma (LUSQ) and its control of cancer-promoting genes in LUSQ cells. The downregulation of miR-150-3p in LUSQ tissues was confirmed by data in The Cancer Genome Atlas (TCGA). The ectopic expression of miR-150-3p attenuated cancer cell aggressive features, e.g., cell cycle arrest, migration and invasive abilities. Our target search strategy successfully identified a total of 49 putative targets that were listed as subjects of miR-150-3p regulation in LUSQ cells. Interestingly, among these targets, 17 genes were categorized as related to the "cell cycle" based on Gene Ontology (GO) classification, namely CENPA, CIT, CCNE1, CCNE2, TIMELESS, BUB1, MCM4, HELLS, SKA3, CDCA2, FANCD2, NUF2, E2F2, SUV39H2, CASC5, ZWILCH and CKAP2). Moreover, we show that the expression of HELLS (helicase, lymphoid specific) is directly controlled by miR-150-3p, and its expression promotes the malignant phenotype of LUSQ cells. [ABSTRACT FROM AUTHOR]

CD44, a non-kinase cell surface transmembrane glycoprotein, has been widely implicated as a cancer stem cell (CSC) marker in several cancers. Cells overexpressing CD44 possess several CSC traits, such as self-renewal and epithelial-mesenchymal transition (EMT) capability, as well as a resistance to chemo- and radiotherapy. The CD44 gene regularly undergoes alternative splicing, resulting in the standard (CD44s) and variant (CD44v) isoforms. The interaction of such isoforms with ligands, particularly hyaluronic acid (HA), osteopontin (OPN) and matrix metalloproteinases (MMPs), drive numerous cancer-associated signalling. However, there are contradictory results regarding whether high or low CD44 expression is associated with worsening clinicopathological features, such as a higher tumour histological grade, advanced tumour stage and poorer survival rates. Nonetheless, high CD44 expression significantly contributes to enhanced tumourigenic mechanisms, such as cell proliferation, metastasis, invasion, migration and stemness; hence, CD44 is an important clinical target. This review summarises current research regarding the different CD44 isoform structures and their roles and functions in supporting tumourigenesis and discusses CD44 expression regulation, CD44-signalling pathways and interactions involved in cancer development. The clinical significance and prognostic value of CD44 and the potential of CD44 as a therapeutic target in cancer are also addressed. [ABSTRACT FROM AUTHOR]

Simple Summary: One way to facilitate the detection of early malignant transformation processes in oral potentially malignant disorders, including oral leukoplakia, involves the parallel evaluation of tissue and saliva biomarkers, as such indicators may elucidate both protein CD44 expression in leukoplakia tissue and its soluble form and total protein detection in saliva. We concluded that the OncAlert® Oral Cancer Rapid test is a non-invasive and simple but only screening method which can complement clinical diagnostics methods in daily clinical practice when considering oral leukoplakia, most importantly, in order to obtain information about the potential for early malignancy. The aim of this study was to determine whether and how pan-CD44 protein expression in leukoplakia tissues correlates with positive SolCD44 test presence and their role in oral leukoplakia. SolCD44 and total protein expression in saliva were determined using an OncAlert® Oral Cancer Rapid test. Comparison of paired associations of total protein, SolCD44, mean number of CD44 expressed epithelial layers in leukoplakia tissue, and macrophages below the basement membrane between control group and patients with leukoplakia showed statistically significant results (p < 0.0001). It is shown that the total protein indicates low or elevated risk of possible malignant transformation processes in leukoplakia. Statistically significant differences between higher total protein level and clinical forms of oral leukoplakia (p < 0.0001), as well as CD44-labeled epithelial cell layer decrease (p < 0.0001), were found. This possibly points to the onset of the stemness loss in leukoplakia tissue. CD9 antigen expression in the exosomes of the oral epithelium explained the intercellular flow of SolCD44 and other fluids in the leukoplakia area. We conclude that the OncAlert® Oral Cancer Rapid test is a valuable screening method in daily clinical practice, in terms of complementing clinical diagnostics methods and to assess the potential for early malignancy. [ABSTRACT FROM AUTHOR]