Search Results (347)

Background: Autism spectrum disorder (ASD) represents a neurobiological disorder with a high prevalence in the children’s population. The aim of the present review was to assess the current evidence on the use of salivary biomarkers for the early diagnosis of ASD. Materials and methods: A search was conducted on the electronic databases PUBMED/Medline, Google Scholar and Scopus for the retrieval of articles concerning the study topic. Results: A total of 22 studies have been included in the present review considering 21 articles identified from databases and 1 article included using a manual search. A wide range of biomarkers have been proposed for early detection of ASD diseases including nonspecific inflammation markers like interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor α (TNFα), oxidative stress markers like superoxide dismutase and glutathione peroxidase, hormones such as cortisol and oxytocin, various microRNAs including miR-21, miR-132 and miR-137, and exosomes. The techniques used for biomarke detection may vary according to molecule type and concentration. Conclusions: salivary biomarkers could represent a potential useful tool for the primary detection of several systemic diseases including ASD, taking advantage of non-invasiveness and cost-effective capability compared to other biofluid-based diagnostic techniques. Full article

Background: The majority of parotid gland tumors are benign, e.g., pleomorphic adenoma (PA) and Warthin’s tumor (WT). From a biomedical point of view, oxidative stress is of significant importance due to its established association with the initiation and progression of various types of cancer, including parotid gland cancers. This study aimed to assess whether blood prooxidant–antioxidant markers could aid in diagnosing and guiding surgery for recurrent malignancies after parotid tumor treatment. Methods: We examined patients (n = 20) diagnosed with WT (n = 14) and PA (n = 6) using histopathological verification and computed tomography (CT) who qualified for surgical treatment. Blood samples were taken before the surgery and again 10 days later for biochemical analysis. The activities of the antioxidant enzymes (SOD, CAT and GPx), the non-enzymatic antioxidants (GSH and UA) and oxidative stress markers (MDA and TOS) were determined in the blood. The activities of CK and LDH and the concentrations of Cor and TAS were measured in the serum. Hb and Ht were determined in whole blood. Results: The patients’ SOD, CAT, and GPx activities after surgery did not differ significantly from their preoperative levels. However, following surgery, their serum TOS levels were significantly elevated in all the patients compared to baseline. In contrast, the plasma MDA concentrations were markedly reduced after surgery. Similarly, the GSH concentrations showed a significant decrease postoperatively. No significant changes were observed in the CK and LDH activities, TAS concentrations, or levels of Hb, Ht and Cor following surgery. Conclusions: The surgical removal of salivary gland tumors did not result in a reduction in oxidative stress at 10 days after surgery. Therefore, further studies are needed to determine the effectiveness of endogenous defense mechanisms in counteracting the oxidative stress induced by salivary gland tumors. Full article

Background/Objectives: Taste dysfunction is a highly prevalent yet underrecognized complication among patients with head and neck cancer (HNC), significantly impairing nutritional intake, treatment adherence, and quality of life (QoL). This comprehensive review synthesizes current knowledge on the pathophysiological mechanisms and clinical management of taste dysfunction associated with HNC and its treatments, particularly chemotherapy and radiotherapy. Methods: A structured literature search was performed across PubMed, Scopus, and Cochrane Library for articles published between January 2015 and February 2025. Studies were included if they investigated taste dysfunction related to HNC, focusing on pathophysiological mechanisms and therapeutic interventions. A total of 47 original studies were analyzed through a narrative synthesis due to heterogeneity in study designs and outcomes. Results: Taste dysfunction in HNC patients arises from tumor-related inflammation, cytotoxic injury from chemotherapy, and radiation-induced epithelial and neural damage. Chemotherapy and radiotherapy often exert synergistic negative effects on gustatory function. Management strategies identified include dietary counselling, nutritional supplementation (zinc, lactoferrin, monosodium glutamate, miraculin), pharmacological agents targeting salivary function, and non-pharmacological interventions such as acupuncture, photobiomodulation, and reconstructive surgery. However, the evidence is limited by small sample sizes, methodological variability, and the frequent exclusion of HNC patients from broader dysgeusia trials. Reported prevalence of taste dysfunction ranged from 39% to 97.4%, with higher rates observed among patients treated with radiotherapy and chemoradiotherapy. Conclusions: Taste dysfunction remains a critical yet unmet clinical challenge in HNC patients. High-quality, targeted research is urgently needed to develop standardized assessments and evidence-based management strategies to improve patient outcomes. Full article

Background/Objectives: Mucoepidermoid carcinoma (MEC) is the most common malignant tumor of the salivary glands. Metastatic spread occurs in up to 80% of high-grade tumors; however, the mechanisms underlying this process are largely unknown. Large-scale microRNA (miRNA) expression profiling studies of human cancers have demonstrated that dysregulation of miRNA is frequently associated with many cancer types. This study aimed to investigate the miRNA profiles of metastatic and non-metastatic MECs. Methods: Using real-time RT-PCR (qPCR), we analyzed the expression of 377 miRNAs in four non-metastatic MECs, three MECs with lymph node metastasis, three MECs with distant metastasis, and two non-neoplastic human salivary glands. To identify differentially expressed miRNAs, bioinformatics analysis was performed using hierarchical clustering analysis. Results: The miRNA profile discriminated between non-neoplastic and tumor samples and between metastatic and non-metastatic tumors. Twelve miRNAs were differentially expressed between non-neoplastic and non-metastatic MECs. MEC analysis of non-neoplastic and lymph node metastases demonstrated that 10 miRNAs were differentially expressed. In non-neoplastic versus distant metastatic MECs, three miRNAs were differentially expressed: one downregulated and two upregulated. By comparing non-metastatic MECs with lymph node metastatic MECs, we identified 17 upregulated miRNAs. Considering non-metastatic MECs versus distant metastatic MECs, two miRNAs were upregulated. One miRNA was differentially expressed between lymph node metastatic and distant metastatic MECs. Conclusions: Our findings indicated that miRNA profiles may serve as valuable biomarkers for distinguishing the metastatic potential of salivary MECs, warranting further investigation to validate their utility in clinical practice. Full article

Background/Objectives: Pleomorphic adenomas (PAs) are the most common salivary gland tumors, with a known risk of recurrence, especially after inadequate surgical excision. Understanding how surgical approach influences recurrence remains essential to optimize management. This study aimed to synthesize recurrence rates of PAs based on different surgical techniques and to illustrate the implications of surgical strategy through a representative case of multifocal deep lobe recurrence. Methods: A systematic review was conducted according to PRISMA 2020 guidelines. Three electronic databases (PubMed, Cochrane, and Google Scholar) were searched for studies published in the last ten years, reporting recurrence rates of PAs by surgical approach. Data were extracted on recurrence, complications, and tumor characteristics. Additionally, a complex clinical case of recurrent deep lobe PA (DLPA) was presented to contextualize the findings. Results: Fifteen studies were included, comprising a total of 2095 patients. Recurrence rates were 3.27% after extracapsular dissection (ED), 0.73% after partial superficial parotidectomy (PSP), and 2.41% after superficial parotidectomy (SP). Recurrent PA (RPA) is often multifocal and associated with increased risks of facial nerve palsy and positive surgical margins. The presented case involved five surgical procedures, with ultimate total parotidectomy and facial nerve preservation despite infiltrative recurrence in the prestyloid space. Conclusions: Techniques such as ED and PSP have demonstrated their efficacy and safety compared to more invasive approaches, although their application should be carefully evaluated based on tumor size and location. RPA remains a challenging entity to treat. Avoiding outdated techniques and ensuring evidence-based decision making may improve long-term outcomes in PA management. Full article

Anxiety and depression are highly prevalent mental health disorders often associated with dysregulation of neuroendocrine and immune systems, particularly the hypothalamic–pituitary–adrenal (HPA) axis and the sympathetic–adrenal–medullary (SAM) system. Recent research highlights the potential of salivary biomarkers to serve as non-invasive indicators for psychological distress. This narrative review synthesizes current evidence on key salivary biomarkers, cortisol, alpha-amylase (sAA), secretory immunoglobulin A (sIgA), chromogranin A (CgA), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), brain-derived neurotrophic factor (BDNF), and salivary microRNAs (miRNAs), in relation to anxiety, depression, and stress. A comprehensive literature search (2010–2025) was conducted using multiple databases and relevant MeSH terms. The review reveals consistent associations between these salivary analytes and stress-related disorders, reflecting changes in neuroendocrine activity, immune response, and neuroplasticity. Cortisol and sAA mirror acute stress reactivity, while cytokines and CRP indicate chronic inflammation. BDNF and miRNAs provide insight into neuroplastic dysfunction and gene regulation. Despite promising results, limitations such as variability in sampling methods and biomarker specificity remain. In conclusion, salivary biomarkers offer a promising avenue for early detection, monitoring, and personalization of treatment in mood and anxiety disorders. Conclusions: Cortisol and alpha-amylase serve as the principal markers of acute stress response, whereas cytokines such as IL-6 and TNF-α, together with CRP, indicate chronic inflammation associated with extended emotional distress. Full article

Childhood obesity and overweight are linked to subclinical inflammatory conditions. The present manuscript aimed to undertake a scoping review exploring the relationship between childhood obesity and salivary biomarkers to answer the following question: “Are salivary biomarkers trustful factors/indicators for childhood obesity?” The main search terms used were: “obesity and salivary biomarkers and children” (Pubmed, Scielo, Scopus, Embase databases: 1999–2025). Assessed articles were carefully classified according to a predetermined criterion (Newcastle–Ottawa Scale), and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were considered. Papers involving children >13 years, duplicates/triplicates, literature reviews, and non-related to the question addressed were excluded. More than 30 salivary biomarkers were assessed in the thirteen studies appraised. Three studies were rated as having a high level of evidence, two as moderate, and eight as having a low level. Fourteen biomarkers were found to be significantly increased in childhood obesity/overweight (p < 0.05): leptin, insulin, α-amylase, tumor necrosis factor α, interleukin 6, vascular endothelial growth factor-A, C-reactive protein, monocyte chemotactic protein-1, resistin, phosphate, nitric oxide, interleukin 1β, uric acid and fetuin-A; and three were found to be significantly decreased (p < 0.05): adiponectin, secretory immunoglobulin A, and interleukin-12p70. In conclusion, the present review supported the idea that saliva might be a promising diagnostic tool in early life and that it is a significant source of obesity biomarkers in children. Full article

Background/Objectives: The purpose of this study was to determine the incidence of salivary gland tumors based on age, gender, histological type, and localization over an eleven-year period at the University Hospital of Split. Methods: The medical records of the Department of Otorhinolaryngology with Head and Neck Surgery and the Department of Maxillofacial Surgery at the University Hospital of Split regarding salivary gland tumors were searched from January 2012 to December 2022. The current fifth World Health Organization (WHO) Classification of Head and Neck Tumors and its criteria were considered during that process. Results: Out of 404 patients, 211 (52.20%) were female and 193 (47.77%) male. The mean age was 60. There were four pediatric patients. Six patients had a combination of two different histological types of salivary gland tumors present simultaneously at the exact localization. Therefore, there were 410 histological types in total, 214 related to females and 196 to males. A total of 361 (88.05%) benign and 49 (11.95%) malignant primary salivary gland tumors were detected. The parotid gland was the predominant location (N = 361, 87.8%). There were no cases affecting the sublingual gland. Pleomorphic adenoma was the most common benign histological type (N = 169, 41.2%). The most common malignant histological types were adenoid cystic carcinoma (N = 9, 2.2%) and mucoepidermoid carcinoma (N = 9, 2.2%). The average incidences of salivary gland tumors in the 11 years for the four Dalmatian counties and the Republic of Croatia were 4.45/100,000 and 0.9/100,000, respectively. Conclusions: The results of this study, primarily the ones concerning histological types and localization, do not deviate from general knowledge about salivary gland tumors. Simultaneous and ipsilateral occurrence of different histological types is a rare and extremely valuable finding. The average incidence for Dalmatian counties and the Republic of Croatia is within the range of the International Agency for Research on Cancer estimates. Full article

Salivary gland cancers (SGCs) pose a therapeutic challenge due to their aggressive nature and limited treatment options. Ion transporters, particularly the sodium/iodide symporter (SLC5A5), which transport iodine in the form of iodide anion (I⁻) into cells, have emerged as potential therapeutic targets in tumors of glandular origin. Our research indicates that SLC5A5 is expressed predominantly in ductal cells of human and murine SGC cells. We assessed the effects of potassium iodide (KI), a source of iodide ions. KI treatment reduced SGC cell proliferation and viability without impacting migration. KI increased ROS levels and triggered caspase-dependent apoptosis, as indicated by the upregulation of the pro-apoptotic protein BAX, downregulation of the anti-apoptotic protein Bcl-2, and induction of SGC cell shrinkage. KI did not affect NF-κB or TNF-α and SLC5A5 expression. Adding the antioxidant N-acetylcysteine reversed KI-induced growth inhibition, underscoring ROS-induced oxidative stress’s crucial role in growth inhibition. While KI administered in drinking water to mice increased epidermal growth factor (EGF) expression in non-malignant salivary gland tissues, KI decreased EGF receptor (EGFR) expression in malignant SGC cell cultures, where EGFR signaling is frequently dysregulated in SGCs but promoted AKT phosphorylation. Combining KI and anti-EGFR treatment did not yield synergistic anti-SGC cell effects. The study underscores the therapeutic potential of KI as a standalone treatment in vitro for SGC cells. However, the upregulation of EGF in non-malignant tissues and, therefore, the possibility to enhance EGFR-driven signals and AKT phosphorylation after KI treatment in cancer patients could indicate a risk of rendering SGC cells more drug resistant, warranting further investigation to optimize its clinical application. Full article

Thyroid scintigraphy is a key tool for diagnosing and staging hyperthyroidism in cats, but follow-up scintigraphic studies after radioiodine treatment are limited. This multicentric study evaluated ^99mTc-pertechnetate scintigraphy findings in 234 hyperthyroid cats before and 6 months after radioiodine treatment. Based on serum T4 and TSH concentrations, 165 (70.5%) became euthyroid, 54 (23.1%) had subclinical hypothyroidism, and 15 (6.4%) developed overt hypothyroidism. On post-treatment scintigraphy, all cats showed reduced size and radionuclide uptake of “hot” thyroid nodules. Of 99 cats with unilateral nodules, 60 (61%) recovered function in the contralateral lobe. Among 135 cats with bilateral nodules, both lobes remained visible in 108 (80%). Persistent “hot” nodules with high thyroid/salivary (T/S) ratios or thyroidal pertechnetate uptake (TcTU) occurred in 26 (11%) cats, all of which were euthyroid. Conversely, 24 (10.4%) cats had minimal or absent thyroid tissue with 17 (71%) being hypothyroid, but seven (29%) were euthyroid. As a diagnostic test for iatrogenic hypothyroidism, TcTU showed the highest sensitivity (62.3), with the T/S ratio (7.3) and background-corrected T/S ratio (30.4) being much lower (p < 0.01). While follow-up scintigraphy aids in assessing thyroid tumor destruction and residual function, its diagnostic utility for differentiating euthyroidism and hypothyroidism is limited, especially for cats with mild (subclinical) hypothyroidism. Full article

Background: We investigated the possibility of predicting tumor burden with salivary extracellular RNA (exRNA) biomarkers in gastric cancer patients. Methods: Saliva samples were prospectively collected from 50 gastric cancer patients who underwent gastrectomy with curative intent. Approximately 5 mL of saliva was collected before surgery and on the 5th to 7th days after surgery. The expression of three mRNAs (SPINK7, PPL, and SEMA4B) and two miRNAs (miR140-5p and miR301a) that were previously validated was determined by reverse transcription quantitative real-time PCR. Results: There were significant differences in the pre-operative expression of PPL (p = 0.025), SEMA4B (p = 0.012), and miR140-5p (p = 0.036) between pathologic stage I/II and III/IV groups. The area under the curve (AUC) of each respective multivariable model in predicting stage III/IV, which was adjusted for age and sex, was 75.4% (PPL), 82.5% (SEMA4B), and 75.5% (miR140-5p). In the multivariable model, including all three biomarkers, the AUC was 89.2%. On the other hand, none of the conventional tumor markers (CEA, CA19-9, and CA72-4) could predict tumor burden before surgery. The AUC of the multivariable model, including CEA, CA19-9, and CA72-4, was 67.2%, 66.2%, and 67.4%, respectively. When all three tumor markers were included in the multivariable model, the AUC was 70.5%. Conclusions: Noninvasively detected salivary biomarkers have been shown to have higher diagnostic accuracy than conventional tumor markers detected by invasive blood tests for estimating pre-operative tumor burden. This study demonstrates the potential utility of these biomarkers in pre-operative risk assessment and monitoring surgical treatment response to gastric cancer. Full article

An underlying pro-inflammatory status is related to recurrence and persistence of inflammatory susceptibility in obesity and periodontitis, two of the most prevalent chronic inflammatory diseases. Elevated levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), part of the inflammatory network linking these two conditions, persist even after periodontal treatment, with high salivary cytokine levels being linked to overweight and obesity risk. This trial assessed the effect of a novel composition comprising olive oil, trimethylglycine and xylitol, delivered topically to the oral mucosa, on salivary cytokines in periodontally healthy normal and overweight/pre-obese individuals. In a randomized placebo-controlled double-blind clinical trial, adult patients were randomly assigned to use a test toothpaste (intervention group, IG) or a placebo toothpaste (control group, CG) three times a day for 1 month. Primary outcomes were levels of salivary cytokines IL-1β, TNF-α and interleukin-4 (IL-4). Significant differences between IG and CG were observed for IL-1β (p = 0.003; Z = 2.901; r = 0.62) and TNF-α (p = 0.001; Z = 3.23; r = 0.69), but not for IL-4 (p = 0.203; Z = 1.321; r = 0.28). A significant reduction in IL-1β (p = 0.008) and a near significant reduction in TNF-α (p = 0.059) was found in the IG at the end of the trial. Additionally, the effect of body mass index on cytokine levels response was analyzed. A significantly different behavior was shown between IG and CG in the overweight/pre-obesity subgroup for IL-1β (p = 0.014; Z = 2.430; r = 0.63) and TNF-α (p = 0.029; Z = 2.199; r = 0.57). Moreover, a significant decrease in IL-1β in the IG (p = 0.028) was observed. The rapid reduction in IL-1β and TNF-α after 1 month of use of the intervention composition suggests a safe and effective novel strategy for reducing pro-inflammatory cytokines that may offer an opportunity to diminish the inflammatory status in patients with overweight/pre-obesity. Full article

Background and clinical significance: Polymorphous adenocarcinoma of the oral cavity is predominantly located in the palate. It is characterized by a slow rate of growth and thus may be misdiagnosed as a benign tumor. Its histology is intricate with other salivary malignancies, thus necessitating specific immunohistochemical stains. Our case report illustrates an adenocarcinoma localized in the palate of a 61-year-old female patient. Case presentation: The patient came to the postgraduate clinic of Oral Medicine and Pathology, Department of Oral Medicine and Pathology, School of Dentistry, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece and provided written informed consent for the subsequent examination. The patient complained about the presence of a mass on the palate, which was otherwise asymptomatic, without being able to pinpoint when the tumor initially emerged. The lesion was biopsied and the histology suggested the immunophenotype p63+/p40- which constitutes an important diagnostic clue for polymorphous adenocarcinoma. The patient was referred to the Department of Oral and Maxillofacial Surgery. Conclusions: The standard therapeutic approach primarily involves surgical excision. The goal is to achieve optimal patient outcome while minimizing unnecessary morbidity. As surgical techniques and understanding of the disease continue to advance, it is crucial for healthcare providers to stay informed and integrate these developments into practice to improve treatment outcomes for patients. Full article

Notch-mediated signaling pathways represent a system that is conserved from an evolutionary point of view, demonstrating a key role in determining cell fate in development; in fact, Notch operates at multiple levels during tissue and organ organization, intervening in the key processes of organogenesis. As a consequence of this, a dysregulation of the Notch-mediated pathways leads to the onset of various pathological conditions such as autoimmune diseases or tumors. The activation of Notch-mediated molecular pathways has also been demonstrated in the development of salivary glands (SGs) and in associated pathologies. Although the numerous advances made in recent years have clarified various aspects of the activation of transductional cascades involving Notch in SGs development and diseases, there are still many aspects that require experimental investigation. In this review, we report, for therapeutic purposes, what is present in the literature relating to the mechanisms regulating the development of Notch-mediated SGs and the most recent discoveries relating to SGs pathologies that derive from alterations of the Notch-mediated pathways. Full article

Background/Objectives: Mucoepidermoid carcinoma (MEC) is the most common malignant tumor of the minor salivary glands, often affecting the hard palate. Preoperative diagnosis and surgical planning are challenging due to anatomical complexity and limitations in sampling, generally obtained by fine-needle aspiration (FNA). This study retrospectively evaluated the diagnostic and therapeutic performance of a high-definition ultrasound (HDUS)-guided fine-needle aspiration cytology/biopsy (FNAC/FNAB) protocol in diagnosing intraoral MEC, based on the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC), with the relative clinical outcomes. Methods: A cohort of 64 patients with histologically confirmed MEC of the minor salivary glands, treated between 2000 and 2022, was retrospectively analyzed. All patients underwent HDUS-guided FNAC/FNAB, imaging (CT, MRI, and panoramic X-ray), and subsequent surgical treatment. The cytological specimens were classified using the MSRSGC. Surgical margins, histopathological findings, lymph node status, and follow-up outcomes were recorded. Results: Of 64 MECs, 42 cases were finally diagnosed as low-grade (LG)/intermediate grade (IG) and 22 as high-grade (HG) carcinomas, using a two-tier histological classification system. HDUS accurately delineated the lesion size, infiltration depth, and bone proximity, with excellent correlation with surgical specimens (difference ≤ 0.6 mm). MSRSGC classification distributed the cases across all categories, with 28 classified as malignant (category VI). Repeat FNAC improved the diagnostic yield in non-diagnostic and atypical cases. FNAB confirmed the cytological findings in all cases, with immunohistochemistry investigation with Ki-67 supporting tumor grading. Surgical margins were clear in all resections. Lymph node metastases were identified in all patients who underwent neck dissection (n = 18), all with HG-MEC. No recurrences occurred among the LG/IG-MEC patients during a median 2-year follow-up. Conclusions: The combined use of HDUS and FNAC/FNAB, interpreted through the MSRSGC framework, offers a highly accurate, minimally invasive approach for preoperative diagnosis and surgical planning in intraoral MEC. HDUS-guided cytology significantly improves diagnostic reliability, particularly in LG/IG and cystic variants, facilitating tailored surgical management. Also, the clinical outcomes may support the possibility of using a simplified grading classification for two histopathological types. Full article