Sign in to use this feature.

Years

Between: -

Subjects

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Journals

Article Types

Countries / Regions

Search Results (113)

Search Parameters:
Keywords = salivary gland pathologies

Order results
Result details
Results per page
Select all
Export citation of selected articles as:
15 pages, 15798 KB  
Article
Targeting Ferroptosis to Restore Salivary Gland Homeostasis in an Obesity Model
by Gi Cheol Park, Hanaro Park, Soo-Young Bang, Ji Min Kim, Sung-Chan Shin, Yong-il Cheon, Ha-Nee Kwon, Jung Hwan Cho and Byung-Joo Lee
Int. J. Mol. Sci. 2026, 27(1), 514; https://doi.org/10.3390/ijms27010514 - 4 Jan 2026
Viewed by 369
Abstract
Obesity is a systemic metabolic disorder that is known to impair various organ systems; however, its precise impact on salivary gland homeostasis remains unclear. Recent studies have implicated ferroptosis—an iron-dependent form of regulated cell death characterized by lipid peroxidation and oxidative stress—in glandular [...] Read more.
Obesity is a systemic metabolic disorder that is known to impair various organ systems; however, its precise impact on salivary gland homeostasis remains unclear. Recent studies have implicated ferroptosis—an iron-dependent form of regulated cell death characterized by lipid peroxidation and oxidative stress—in glandular dysfunction. In this study, we used leptin-deficient (ob/ob) mice to elucidate the role of ferroptosis in obesity-associated salivary gland pathology. The protective effects of ferroptosis inhibition were evaluated by administering ferrostatin-1 (a lipid reactive oxygen species [ROS] scavenger) and deferoxamine (an iron chelator) for an 8-week period. Obese mice exhibited significantly increased body weight, food intake, and hyperglycemia. These systemic changes are accompanied by profound histological alterations in the salivary glands, including lipid droplet accumulation, acinar atrophy, and mitochondrial ultrastructural damage. These alterations correlate with the hallmarks of ferroptotic injury, including increased ROS levels (p < 0.001), elevated malondialdehyde levels (p < 0.01), suppressed glutathione peroxidase 4 activity (p < 0.01), and iron overload (p < 0.001). Salivary gland fibrosis, inflammation, and secretory dysfunction were evident, characterized by the upregulation of TGF-β (p < 0.01) and Collagen I (p < 0.05), reduced expression of aquaporin-5 and amylase, and dysregulated levels of autophagy-related markers (LC3B and p62). Treatment with either ferrostatin-1 or deferoxamine significantly mitigated these pathologies; however, the degree of efficacy varied depending on the specific parameters that were examined. Thus, our findings implicate ferroptosis as a critical contributor to salivary gland dysfunction in obesity and suggest that pharmacological inhibition of this pathway represents a viable therapeutic strategy for preserving glandular integrity under metabolic stress. Full article
(This article belongs to the Special Issue Ferroptosis, ROS and Cell Death Cytomodulator Compounds)
Show Figures

Figure 1

24 pages, 827 KB  
Review
A Narrative Review of Salivary Gland Extracellular Matrix and Sjögren’s Syndrome: Research Status and Future Prospects
by Haodong Su, Xinying Fan, Chunxia Nie, Xiaoyu Tang, Jingjin Hu, Ke Xu, Liyun Zhang and Dan Ma
Biomolecules 2026, 16(1), 72; https://doi.org/10.3390/biom16010072 - 1 Jan 2026
Viewed by 446
Abstract
Sjögren’s syndrome (SS) is a chronic systemic autoimmune disease characterized by the main clinical manifestation of oral and ocular dryness, predominantly affecting middle-aged and elderly women. As the most commonly affected target organs in SS, pathological changes in the salivary glands (SGs) and [...] Read more.
Sjögren’s syndrome (SS) is a chronic systemic autoimmune disease characterized by the main clinical manifestation of oral and ocular dryness, predominantly affecting middle-aged and elderly women. As the most commonly affected target organs in SS, pathological changes in the salivary glands (SGs) and their underlying mechanisms are of great significance for understanding the disease progression. Recent studies have revealed that a dynamic imbalance of the extracellular matrix (ECM) in the SGs plays a crucial role in the pathogenesis of SS. Dysregulation of matrix metalloproteinases (MMPs) and the fibrotic processes they mediate constitute the core pathological changes. These alterations intertwine with local chronic inflammatory responses, cellular senescence, and hyperosmolarity, collectively leading to the destruction of the SG parenchymal structure and progressive loss of secretory function, significantly impairing the patients’ quality of life. However, research on the pathological mechanisms of the SG ECM remains insufficient, and there are currently no specific therapeutic interventions targeting ECM alterations in clinical practice. This review systematically elucidates the characteristics of pathological and physiological changes in the SG ECM in SS and thoroughly explores novel therapeutic strategies based on ECM regulation, as well as their clinical application prospects. Full article
(This article belongs to the Section Molecular Medicine)
Show Figures

Figure 1

16 pages, 4321 KB  
Article
Correlated Expression of Notch2 and ADAM17 in Primary Sjögren’s Syndrome Salivary Glands
by Margherita Sisto, Sabrina Lisi, Roberto Tamma, Michelina De Giorgis, Giuseppe Ingravallo, Mario Della Mura, Joana Sorino, Eliano Cascardi and Domenico Ribatti
J. Clin. Med. 2026, 15(1), 182; https://doi.org/10.3390/jcm15010182 - 26 Dec 2025
Viewed by 305
Abstract
Background/Objectives: The Notch–ADAM17 pathway is a fundamental signaling mechanism where ADAM17, a disintegrin and metalloprotease, cleaves the Notch receptor after the Notch receptor binds to a ligand. Crosstalk between Notch and ADAM17 is often altered in pathological situations. Alterations in Notch2 expression, [...] Read more.
Background/Objectives: The Notch–ADAM17 pathway is a fundamental signaling mechanism where ADAM17, a disintegrin and metalloprotease, cleaves the Notch receptor after the Notch receptor binds to a ligand. Crosstalk between Notch and ADAM17 is often altered in pathological situations. Alterations in Notch2 expression, in particular, appears to be correlated with the onset of various autoimmune diseases. In primary Sjögren’s disease (pSjD), an autoimmune disorder characterized by chronic inflammation, the role of ADAM17 has been extensively explored, but a correlation with Notch2 has not yet been evaluated. Methods: To analyze the gene and protein expression of Notch2 in pSjD and a possible correlation with ADAM17 expression and with the patient’s inflammatory grade, we employed an integrated co-detection protocol to analyze salivary gland tissue sections by combining in situ hybridization (ISH) with immunohistochemistry (IHC). Results: combined ISH/IHC allows us to demonstrate an increased expression of Notch2 mRNA and protein in pSjD salivary glands (SGs) biopsies, which appears correlated with an increased expression of ADAM17, both in acinar and duct cells and in infiltrating lymphocytes. Notch2/ADAM17 expression is higher in biopsies of pSjD SGs characterized by a high degree of inflammation. Conclusions: this work demonstrates the correlated expression in pSjD SGs of ADAM17, which plays multiple roles in the pathogenesis of SjD, and Notch2, widely considered a key player in various inflammatory mechanisms, offering a starting point for future therapeutic interventions to investigate. Full article
(This article belongs to the Special Issue Sjogren’s Syndrome: Clinical Advances and Insights)
Show Figures

Figure 1

11 pages, 1006 KB  
Article
Elevated Flotillin-1 in Saliva and Salivary Glands: A Novel Non-Invasive Biomarker in an Alzheimer’s Disease Mouse Model
by Sunao Kawakami, Cha-Gyun Jung, Rieko Inoue, Tomohisa Nakamura, Soh Sato and Makoto Michikawa
Diagnostics 2026, 16(1), 61; https://doi.org/10.3390/diagnostics16010061 - 24 Dec 2025
Viewed by 418
Abstract
Background/Objectives: Alzheimer’s disease (AD) is currently diagnosed using established biomarkers, such as reduced cerebrospinal fluid (CSF) Aβ42, increased phosphorylated tau, and cerebral amyloid levels detected by PiB-PET. Because these methods are invasive or require specialized facilities, less invasive and easily detectable [...] Read more.
Background/Objectives: Alzheimer’s disease (AD) is currently diagnosed using established biomarkers, such as reduced cerebrospinal fluid (CSF) Aβ42, increased phosphorylated tau, and cerebral amyloid levels detected by PiB-PET. Because these methods are invasive or require specialized facilities, less invasive and easily detectable biomarkers are needed. Flotillin-1 concentrations are reduced in the CSF and serum of patients with AD. This study examined whether flotillin-1 in saliva, a less invasive specimen than blood, could serve as a biomarker. Methods: Wild-type (WT) and AppNL–G–F (APP knock-in; APP-KI) mice were used to create four groups (2 and 9 months of age, six animals per group). Saliva and salivary glands were collected, and flotillin-1 levels were measured using Western blotting. Intracellular signaling pathways regulating flotillin-1 and salivary gland Aβ42 levels were analyzed using Western blotting and ELISA, respectively. Results: Flotillin-1 levels in the saliva and salivary glands were significantly higher in the 9-month-old APP-KI group than in all other groups, including age-matched WT mice. Phosphorylated extracellular signal-regulated kinase (p-ERK) levels were also significantly elevated in the 9-month-old APP-KI group, whereas phosphorylated c-Jun N-terminal kinase (p-JNK) levels did not differ significantly. Salivary gland Aβ42 levels were markedly increased only in the 9-month-old APP-KI group. Conclusions: Flotillin-1 levels in saliva and salivary glands were significantly elevated in the presence of AD pathology. Aβ accumulation in the salivary glands likely activates the ERK signaling cascade, promoting flotillin-1 expression and secretion. Thus, salivary flotillin-1 may serve as a promising noninvasive biomarker for the early diagnosis of Alzheimer’s disease. Full article
(This article belongs to the Section Clinical Laboratory Medicine)
Show Figures

Figure 1

24 pages, 9596 KB  
Article
Benign Epithelial Salivary Neoplasms: Single-Centered Histopathologic and Clinicodemographic Romanian Retrospective Study
by Constantin Aleodor Costin, Adriana Grigoraș, Elena Corina Andriescu and Cornelia Amalinei
Clin. Pract. 2025, 15(12), 235; https://doi.org/10.3390/clinpract15120235 - 15 Dec 2025
Viewed by 376
Abstract
Background: Epidemiological studies on benign epithelial salivary gland tumors are challenging due to their rarity, pathological heterogeneity, variable tumor locations, and the limited national data collection in Romania. Our study aimed at the evaluation of benign epithelial salivary gland tumors collected over [...] Read more.
Background: Epidemiological studies on benign epithelial salivary gland tumors are challenging due to their rarity, pathological heterogeneity, variable tumor locations, and the limited national data collection in Romania. Our study aimed at the evaluation of benign epithelial salivary gland tumors collected over fifteen years in a tertiary center, in order to characterize their demographic and histopathological profiles and to contribute to their diagnostic and therapeutic strategies. Materials and Methods: A retrospective analysis of 404 cases of benign epithelial salivary gland tumors diagnosed in “Sf. Spiridon” County Hospital, Iasi, from 2010 to 2024, has been performed. Results: The analyzed cases showed a slight female predominance (52.97%) and a mean patient age of 54.55 ± 14.207 years. Tumor frequency increased progressively with age, peaking in the sixth and seventh decades of life. The most common histological types were pleomorphic adenoma (62.62%) and Warthin tumor (29.95%), both types showing a predominant parotid gland involvement (88.51%). The recurrences were rare, being registered only in 1.58% of pleomorphic adenomas. A significant association between tumor histological type and both gender (p < 0.001) and age group (p < 0.001) was registered, while no significant correlation between gender and age group (p = 0.288) or between tumor location and gender or age group (p = 0.382; p = 0.383) was found. Conclusions: The frequency of pleomorphic adenoma is increasing, showing an age-related distribution and parotid gland propensity. Key morphological features in each histological type support a better preoperative stratification, a more confident margin assessment, and an individualized extent of excision with function preservation. Full article
(This article belongs to the Special Issue Clinical Outcome Research in the Head and Neck: 2nd Edition)
Show Figures

Figure 1

9 pages, 214 KB  
Brief Report
Sjogren Disease and Nephrolithiasis: A Case Series and Review of the Literature
by Ben Schroeder, Chokkalingam Siva and Chen-Chung Steven Liu
Clin. Pract. 2025, 15(12), 225; https://doi.org/10.3390/clinpract15120225 - 28 Nov 2025
Viewed by 759
Abstract
Background: Primary Sjogren Disease (pSD) is a chronic autoimmune disease characterized by a classic triad of keratoconjunctivitis sicca, xerostomia, and polyarthritis. The primary pathological feature of pSD is lymphoplasmacytic infiltration in glandular epithelial tissue, often affecting the salivary and lacrimal glands, leading to [...] Read more.
Background: Primary Sjogren Disease (pSD) is a chronic autoimmune disease characterized by a classic triad of keratoconjunctivitis sicca, xerostomia, and polyarthritis. The primary pathological feature of pSD is lymphoplasmacytic infiltration in glandular epithelial tissue, often affecting the salivary and lacrimal glands, leading to classic sicca symptoms (ocular and oral dryness). Sjogren Disease (SD) can be categorized as “primary” when occurring independently or “secondary” when accompanying another autoimmune connective tissue disorder such as rheumatoid arthritis, systemic lupus erythematosus, or systemic sclerosis. Additionally, systemic disease is common in pSD and can manifest with kidney dysfunction resulting in nephrolithiasis and distal renal tubular acidosis (dRTA). Methods: This report details a case series drawing patients from the literature as well as patients from our institution which serves to demonstrate key points in clinical hallmarks. We utilize a literature search with key words Sjogren Disease, nephrolithiasis, renal tubular acidosis, and nephrocalcinosis in addition to pSD patients with concomitant nephrolithiasis at our institution to characterize clinical and serologic findings as well as treatment modalities. Results: We find well demonstrated clinical hallmarks such as female predominance and presence of dRTA amongst the cohort of pSD patients. We also find that further research on pSD serologies could prove beneficial in risk stratifying those most likely to develop renal disease and nephrolithiasis. Furthermore, we review signs, symptoms, pathophysiology, and management of SD with added emphasis on associated renal disease including nephrolithiasis and dRTA. Conclusion: Overall, pSD associated renal disease remains an area of ongoing research and further study on patient serologies may aid clinicians in better serving and surveilling patients at risk of systemic involvement. Full article
19 pages, 2587 KB  
Article
Assessment of ChatGPT in Recommending Immunohistochemistry Panels for Salivary Gland Tumors
by Maria Cuevas-Nunez, Cosimo Galletti, Luca Fiorillo, Aida Meto, Wilmer Rodrigo Díaz-Castañeda, Shokoufeh Shahrabi Farahani, Guido Fadda, Valeria Zuccalà, Victor Gil Manich, Javier Bara-Casaus and Maria-Teresa Fernández-Figueras
BioMedInformatics 2025, 5(4), 66; https://doi.org/10.3390/biomedinformatics5040066 - 26 Nov 2025
Cited by 1 | Viewed by 841
Abstract
Background: Salivary gland tumors pose a diagnostic challenge due to their histological heterogeneity and overlapping features. While immunohistochemistry (IHC) is critical for accurate classification, selecting appropriate markers can be subjective and influenced by resource availability. Artificial intelligence (AI), particularly large language models (LLMs), [...] Read more.
Background: Salivary gland tumors pose a diagnostic challenge due to their histological heterogeneity and overlapping features. While immunohistochemistry (IHC) is critical for accurate classification, selecting appropriate markers can be subjective and influenced by resource availability. Artificial intelligence (AI), particularly large language models (LLMs), may support diagnostic decisions by recommending IHC panels. This study evaluated the performance of ChatGPT-4, a free and widely accessible general-purpose LLM, in recommending IHC markers for salivary gland tumors. Methods: ChatGPT-4 was prompted to generate IHC recommendations for 21 types of salivary gland tumors. A consensus of expert pathologists established reference panels. Each tumor type was queried using a standardized prompt designed to elicit IHC marker recommendations (“What IHC markers are recommended to confirm a diagnosis of [tumor type]?”). Outputs were assessed using a structured scoring rubric measuring accuracy, completeness, and relevance. Agreement was measured using Cohen’s Kappa, and diagnostic performance was evaluated via sensitivity, specificity, and F1-scores. Repeated-measures ANOVA and Bland–Altman analysis assessed consistency across three prompts. Results were compared to a rule-based system aligned with expert protocols. Results: ChatGPT-4 demonstrated moderate overall agreement with the pathologist panel (κ = 0.53). Agreement was higher for benign tumors (κ = 0.67) than for malignant ones (κ = 0.40), with pleomorphic adenoma showing the strongest concordance (κ = 0.74). Sensitivity values across tumor types ranged from 0.25 to 0.96, with benign tumors showing higher sensitivity (>0.80) and lower specificity (<0.50) observed in complex malignancies. The overall F1-score was 0.84 for benign and 0.63 for malignant tumors. Repeated prompts produced moderate variability without significant differences (p > 0.05). Compared with the rule-based system, ChatGPT included more incorrect and missed markers, indicating lower diagnostic precision. Conclusions: ChatGPT-4 shows promise as a low-cost tool for IHC panel selection but currently lacks the precision and consistency required for clinical application. Further refinement is needed before integration into diagnostic workflows. Full article
(This article belongs to the Special Issue The Application of Large Language Models in Clinical Practice)
Show Figures

Graphical abstract

22 pages, 1654 KB  
Systematic Review
Giant Asymptomatic Submandibular Sialolith: A Case Report Accompanied by Systematic Review
by Renato Gomes Azevedo, Luan Felipe Toro, Vinícius Franzão Ganzaroli, Vinícius José Ifanger, Nathan Ayres de Faria, Rodrigo Ubiali de Rezende, Julia da Conceição Francisquini and Gestter Willian Lattari Tessarin
Clin. Pract. 2025, 15(11), 205; https://doi.org/10.3390/clinpract15110205 - 10 Nov 2025
Viewed by 912
Abstract
Background/Objectives: Salivary stones, also known as sialoliths, are calcified structures that develop within the salivary glands and/or their ducts. They occur in approximately 1 per 10,000 to 30,000 individuals per year, primarily affecting adults between 30 and 50 years of age. Although several [...] Read more.
Background/Objectives: Salivary stones, also known as sialoliths, are calcified structures that develop within the salivary glands and/or their ducts. They occur in approximately 1 per 10,000 to 30,000 individuals per year, primarily affecting adults between 30 and 50 years of age. Although several hypotheses have been proposed, the exact mechanisms of formation and their predisposing factors are yet to be confirmed. The submandibular gland is the most commonly affected site, accounting for nearly 80% of cases, while giant and asymptomatic sialoliths are rare clinical findings in dental practice. This study is divided into two components: first, a case report of a giant, asymptomatic sialolith located in Wharton’s duct; second, a systematic review of the literature to explore the clinical procedures, diagnoses, outcomes, and other relevant aspects of this pathology. Methods: The case involved a 42-year-old woman who sought dental care due to the presence of a painless sublingual swelling. Intraoral examination and imaging revealed a calcified mass consistent with sialolithiasis in Wharton’s duct. The stone was successfully removed via sialolithotomy. For the systematic review, an extensive search was conducted in PubMed, Embase, and Cochrane Library up to June 2025, using specific keywords. Initially, 262 studies were identified. After applying inclusion and exclusion criteria, six case reports were included in the final analysis. Results: All selected studies described giant salivary stones located in Wharton’s duct and/or the parenchyma of the submandibular gland, notably without associated pain. Computed tomography and ultrasonography were the most commonly used imaging modalities for diagnosis. In all cases, the primary treatment was sialolithotomy. Conclusions: This study explored a rare case report of an asymptomatic giant sialolith in Wharton’s duct, and it includes a systematic review focused exclusively on asymptomatic giant sialoliths. It specifically addresses key characteristics, preferred imaging modalities, treatment strategies, and clinical considerations for managing this uncommon condition. Registration number: Prospero registration nº CRD420251076737. Full article
Show Figures

Graphical abstract

24 pages, 1757 KB  
Article
Parotid Gland Tumors: An Institutional 8-Year Retrospective Study Spanning the COVID-19 Pandemic and Global Diagnostic Trends
by Eduard Gidea-Paraschivescu, Ruxandra Elena Luca, Cristian Adrian Ratiu and Ciprian Ioan Roi
J. Clin. Med. 2025, 14(20), 7382; https://doi.org/10.3390/jcm14207382 - 19 Oct 2025
Cited by 1 | Viewed by 1232
Abstract
Background/Objectives: Despite the relative rarity of salivary gland tumours (SGT), they are a complex and challenging pathology. This is primarily due to the complexity of surgical treatment, the difficulty of diagnosis, and the sometimes ambiguous prognosis. Methods: This retrospective study examined parotid [...] Read more.
Background/Objectives: Despite the relative rarity of salivary gland tumours (SGT), they are a complex and challenging pathology. This is primarily due to the complexity of surgical treatment, the difficulty of diagnosis, and the sometimes ambiguous prognosis. Methods: This retrospective study examined parotid gland tumors in patients admitted for diagnosis and treatment at the Municipal Hospital of Timisoara–Oral and Maxillofacial Surgery Clinic, Romania, from 2016 to 2023, with the objective of verifying the hypothesis regarding the increasing incidence of benign tumors in the major salivary glands, particularly the parotid gland. Results: A total of 207 consecutive parotid nodular lesion cases were analysed, with 186 having a histopathological analysis. The findings encompass demographic patterns, temporal dynamics, histopathological profiles, malignancy characteristics, and statistical associations. The cohort was evenly distributed by sex (102 females, 105 males) with a median age of 58 years (IQR: 46–69). The largest age group was ≥60 years (n = 99; 47.8%), followed by 40–59 years (n = 76; 36.7%) and <40 years (n = 32; 15.5%). No significant sex difference in age distribution was observed. Annual case volumes showed a high plateau between 2017–2019 (40–41 cases/year), then fell sharply during the pandemic (2020–2022), reaching a nadir in 2021 (11 cases). A partial rebound occurred in 2023 (21 cases). The relative proportion of malignant diagnoses remained stable between pre-pandemic (20.0%) and pandemic/post-pandemic (8.9%) intervals, consistent with prioritization of oncologic surgeries during service restrictions. Benign tumors predominated (n = 126; 60.9%), led by pleomorphic adenoma (n = 64; 50.8% of benign) and Warthin tumor (n = 59; 46.8% of benign). Malignant tumors accounted for 31 cases (15.0%), most commonly squamous cell carcinoma (n = 6), mucoepidermoid carcinoma (n = 6), and adenocarcinoma of salivary origin (n = 5). Mann–Whitney U tests confirmed no significant differences in median age between malignant and benign cases, or between pre-pandemic and pandemic/post-pandemic intervals. Odds ratios suggested clinically relevant but non-significant increases in malignancy risk for males (OR ≈ 2.1) and for patients ≥60 years (OR ≈ 1.2). Linear regression of annual case counts revealed a downward slope of –3.5 cases/year (p ≈ 0.074), driven by the sharp pandemic-era decline. Conclusions: This study illustrates that, despite a significant decrease in surgical case volume during the COVID-19 pandemic, the relative distribution of parotid tumor pathology remained stable. Malignant lesions mostly occurred in older patients and males, with no statistically significant differences seen among demographic or clinical subgroups. The preservation of consistent malignancy detection rates, despite limited surgical capacity, underscores the efficacy of oncologic prioritization under healthcare disruptions. Full article
Show Figures

Figure 1

9 pages, 4015 KB  
Case Report
A Rare Case Presentation of Intraoral Palatal Myoepithelioma
by Abdullah Saeidi, Albraa Alolayan, Hattan Zaki, Emad Essa, Shadi Alzahrani, Wamiq Fareed and Shadia Elsayed
Reports 2025, 8(4), 196; https://doi.org/10.3390/reports8040196 - 3 Oct 2025
Viewed by 903
Abstract
Background and Clinical Significance: Palatal swellings may originate from various pathological disorders. These swellings may include congenital or acquired factors. The posterior hard palate, which contains many minor salivary glands, is a common site for such swellings. Case Presentation: We present a rare [...] Read more.
Background and Clinical Significance: Palatal swellings may originate from various pathological disorders. These swellings may include congenital or acquired factors. The posterior hard palate, which contains many minor salivary glands, is a common site for such swellings. Case Presentation: We present a rare case of intraoral palatal myoepithelioma in a 45-year-old Egyptian male with a significant history of smoking. Detailed clinical, radiographic, and operative findings are discussed alongside histopathological evaluation, surgical management, and postoperative outcomes. This case highlights the importance of considering myoepithelioma lesions in the differential diagnosis of posterior palatal swelling. Conclusions: Palatal myoepithelioma is a rare but important benign salivary gland tumor that may resemble multiple other intraoral lesions. A complete clinical, radiographic, and histological investigation is required for a definitive diagnosis. Complete surgical excision achieved a favorable outcome. Increased awareness and reporting of this unusual pathology are critical for deepening knowledge and guiding clinical decisions. Full article
Show Figures

Figure 1

27 pages, 5128 KB  
Article
Lepidium meyenii Walpers Promotes the Regeneration of Salivary Gland and Prevents Xerostomia After Irradiation Injury
by Yi-Ting Tsai, Yuan-Chuan Lin, Ming-Jen Cheng, Chun-Ming Shih, Chien-Sung Tsai, Ze-Hao Lai, Ching-Yi Wu, Chen-Wei Liu, Feng-Yen Lin and Yi-Wen Lin
Nutrients 2025, 17(19), 3033; https://doi.org/10.3390/nu17193033 - 23 Sep 2025
Viewed by 1663
Abstract
Objectives: Lepidium meyenii Walpers (LMW), a high-altitude plant, is known to stimulate hormone release, counteract neurodegeneration, and protect against oxidative stress. Saliva is vital for oral health, and reduced production leads to xerostomia, often caused by aging, radiation, or Sjögren’s syndrome. Key pathological [...] Read more.
Objectives: Lepidium meyenii Walpers (LMW), a high-altitude plant, is known to stimulate hormone release, counteract neurodegeneration, and protect against oxidative stress. Saliva is vital for oral health, and reduced production leads to xerostomia, often caused by aging, radiation, or Sjögren’s syndrome. Key pathological features include mesenchymal fibrosis and acinar atrophy, largely regulated by the TGF-β1 pathway. Current treatments are limited, with many patients relying on artificial saliva. Developing therapies to restore salivary function could offer significant benefits. Methods: In this study, we assessed the protective effects of LMW extract (LMWE) in irradiated C57BL/6J mice and TGF-β1-treated rat parotid acinar cells (Par-C10) using histological, molecular, bioenergetic, and 3D organoid analyses to evaluate salivary gland regeneration and lineage-specific differentiation. Results: LMWE significantly restored gland weight, shortened secretion lag time, and increased amylase activity in irradiated mice. Histological and molecular analyses showed reduced acinar atrophy and fibrosis, preservation of epithelial polarity, and upregulation of Mist1, AQP5, and amylase. In vitro, LMWE protected Par-C10 cells from TGF-β1-induced senescence, preserved mitochondrial membrane potential, and improved epithelial barrier function. In 3D organoid cultures of Par-C10 cells embedded in matrix, (1E,4Z)-1-(2,4-dihydroxyphenyl)-5-(3,4-dihydroxyphenyl) penta-1,4-dien-3-one (DHPPD) and (Z)-N-phenyldodec-2-enamide (E4Z-PD)-selectively enhanced acinar and ductal lineage differentiation, respectively. Conclusions: These results suggest that LMWE promotes salivary gland regeneration through antioxidative and lineage-specific mechanisms and may represent a safe and effective therapeutic strategy for xerostomia. Full article
(This article belongs to the Special Issue Diet and Oral Health)
Show Figures

Figure 1

17 pages, 3078 KB  
Article
Ferrostatin-1 Prevents Salivary Gland Dysfunction in an Ovariectomized Rat Model by Suppressing Mitophagy-Driven Ferroptosis
by Gi Cheol Park, Soo-Young Bang, Ji Min Kim, Sung-Chan Shin, Yong-il Cheon, Hanaro Park, Sunghwan Suh, Jung Hwan Cho, Eui-Suk Sung, Minhyung Lee, Jin-Choon Lee and Byung-Joo Lee
Antioxidants 2025, 14(9), 1058; https://doi.org/10.3390/antiox14091058 - 28 Aug 2025
Cited by 1 | Viewed by 1393
Abstract
Salivary gland dysfunction is a common but underexplored complication of menopause that contributes to oral dryness, dysphagia, and increased risk of infection. Although ferroptosis, a form of regulated necrotic cell death driven by iron-dependent lipid peroxidation, has recently been implicated in postmenopausal tissue [...] Read more.
Salivary gland dysfunction is a common but underexplored complication of menopause that contributes to oral dryness, dysphagia, and increased risk of infection. Although ferroptosis, a form of regulated necrotic cell death driven by iron-dependent lipid peroxidation, has recently been implicated in postmenopausal tissue degeneration, its regulatory mechanisms in salivary glands remain unclear. In this study, we investigated the roles of mitochondrial dysfunction and mitophagy in driving ferroptosis-induced salivary gland injury in an ovariectomized (OVX) rat model of estrogen deficiency. OVX rats exhibited elevated markers of oxidative stress, lipid accumulation, and iron overload, and suppression of GPX4 activity in the salivary glands, consistent with ferroptotic activation. These changes were accompanied by impaired mitochondrial dynamics (MFN1 and OPA1), decreased expression of mitochondrial antioxidant regulators (PGC-1α, SOD, and catalase), and upregulation of mitophagy-related genes (PINK1, ULK1, Rab9, and LC3B), as well as LAMP, a lysosomal marker involved in autophagosome–lysosome fusion, while ferritinophagy (NCOA4) remained unchanged. Early administration of ferrostatin-1 effectively suppressed these pathological changes, preserving both glandular structure and function, as evidenced by the restored AQP5 and AMY2A expression. Collectively, our findings reveal that ferroptosis in estrogen-deficient salivary glands is regulated by mitochondrial instability and aberrant mitophagy, and ferrostatin-1 mitigates this cascade through multi-level mitochondrial protection. These results highlight ferrostatin-1 as a promising preventive agent against menopause-associated salivary gland dysfunction, with broader implications for organ-specific ferroptosis modulation. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
Show Figures

Figure 1

21 pages, 1734 KB  
Review
Oculoplastic Interventions in the Management of Ocular Surface Diseases: A Comprehensive Review
by Seyed Mohsen Rafizadeh, Hassan Asadigandomani, Samin Khannejad, Arman Hasanzade, Kamran Rezaei, Avery Wei Zhou and Mohammad Soleimani
Life 2025, 15(7), 1110; https://doi.org/10.3390/life15071110 - 16 Jul 2025
Viewed by 3438
Abstract
This study aimed to comprehensively review surgical interventions for ocular surface diseases (OSDs), including dry eye syndrome (DES), exposure keratopathy, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and ocular graft versus host disease (oGVHD), and to highlight the indications, contraindications, outcomes, and complications [...] Read more.
This study aimed to comprehensively review surgical interventions for ocular surface diseases (OSDs), including dry eye syndrome (DES), exposure keratopathy, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and ocular graft versus host disease (oGVHD), and to highlight the indications, contraindications, outcomes, and complications of various oculoplastic procedures used in their management. A narrative review was performed based on expert-guided selection of relevant studies retrieved from PubMed, Scopus, and Web of Science. Relevant keywords included “ocular surface disease”, “dry eye syndrome”, “exposure keratopathy”, “thyroid eye disease (TED)”, “neurotrophic keratopathy (NK)”, “Stevens-Johnson syndrome”, “toxic epidermal necrolysis”, “punctal occlusion”, “tarsorrhaphy”, “botulinum toxin”, “eyelid loading”, “retractor weakening”, “corneal neurotization (CN)”, “amniotic membrane transplantation (AMT)”, “conjunctival flap”, “ocular graft versus host disease”, and “salivary gland transplantation (SGT)”. Studies addressing surgical approaches for OSDs were included. In conclusion, surgical options for OSDs offer significant benefits when non-invasive treatments fail. Surgical techniques such as punctal occlusion, eyelid fissure narrowing, AMT, and conjunctival flap procedures help stabilize the ocular surface and alleviate symptoms. Advanced methods like CN and SGT target the underlying pathology in refractory cases such as oGVHD. The outcomes vary depending on the disease severity and surgical approach. Each procedure carries specific risks and requires individualized patient selection. Therefore, a tailored approach based on clinical condition, anatomical involvement, and patient factors is essential to achieve optimal results. Ongoing innovations in reconstructive surgery and regenerative medicine are expected to further improve outcomes for patients with OSDs. Full article
Show Figures

Figure 1

13 pages, 786 KB  
Article
Aquaporin mRNA in Human Saliva
by Katharina Rump, Daria Pakosch-Nowak, Andrea Witowski, Bjoern Koos, Dominik Ziehe, Jennifer Orlowski, Michael Adamzik, Martin Kunkel and Markus Baumann
Genes 2025, 16(7), 804; https://doi.org/10.3390/genes16070804 - 8 Jul 2025
Viewed by 900
Abstract
Background: Aquaporins (AQPs) are integral membrane proteins that facilitate water transport across biological membranes. While their role is well-characterized in various tissues, their function in the oral cavity remains poorly understood. Saliva is an easily accessible, non-invasive biofluid that contains stable extracellular RNA [...] Read more.
Background: Aquaporins (AQPs) are integral membrane proteins that facilitate water transport across biological membranes. While their role is well-characterized in various tissues, their function in the oral cavity remains poorly understood. Saliva is an easily accessible, non-invasive biofluid that contains stable extracellular RNA and can reflect both systemic and local physiological or pathological processes, making it a promising source for RNA analyses. This study investigates AQP mRNA levels in human saliva. Methods: Saliva samples were collected from patients of a dental practice and analyzed using quantitative PCR to detect AQP levels. An in silico analysis of AQPs in cells of the oral cavity were performed. Baseline data of the patients were recorded. Results: Our findings demonstrate the presence of multiple AQP subtypes in human saliva. AQP5 was the most abundant, followed by AQP9 and AQP1. The levels of several AQPs showed intercorrelation, whereas AQP3 appeared to be independently regulated and did not correlate with the other AQPs. Conclusions: This study demonstrates that differential AQP mRNA levels can be detected in human saliva. These findings suggest that salivary AQP mRNA may serve as surrogate markers for altered AQP levels in cells of the oral cavity. In the future, such patterns of AQP levels could potentially be used to identify or monitor pathological conditions affecting the oral mucosa or salivary glands. Further studies are required to validate this approach and to understand its diagnostic relevance. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
Show Figures

Figure 1

16 pages, 3450 KB  
Article
Elucidating Regulatory Mechanisms of Genes Involved in Pathobiology of Sjögren’s Disease: Immunostimulation Using a Cell Culture Model
by Daniel D. Kepple, Thomas E. Thornburg, Micaela F. Beckman, Farah Bahrani Mougeot and Jean-Luc C. Mougeot
Int. J. Mol. Sci. 2025, 26(12), 5881; https://doi.org/10.3390/ijms26125881 - 19 Jun 2025
Cited by 1 | Viewed by 1109
Abstract
Sjögren’s disease (SjD) is an autoimmune disease of exocrine tissues. Prior research has shown that ETS proto-oncogene 1 (ETS1), STAT1, and IL33 may contribute to the disease’s pathology. However, the regulatory mechanisms of these genes remain poorly characterized. Our objective was to explore [...] Read more.
Sjögren’s disease (SjD) is an autoimmune disease of exocrine tissues. Prior research has shown that ETS proto-oncogene 1 (ETS1), STAT1, and IL33 may contribute to the disease’s pathology. However, the regulatory mechanisms of these genes remain poorly characterized. Our objective was to explore the mechanisms of SjD pathology and to identify dysfunctional regulators of these genes by immunostimulation of SjD and sicca relevant cell lines. We used immortalized salivary gland epithelial cell lines (iSGECs) from Sjögren’s disease (pSS1) and sicca (nSS2) patients, previously developed in our lab, and control cell line A253 to dose with immunostimulants IFN-γ or poly(I:C) (0 to 1000 ng/mL and 0 to 1000 µg/mL, respectively) over a 72 h time course. Gene expression was determined using qRT-PCR delta-delta-CT method based on glyceraldehyde-3-phosphate dehydrogenase (GAPDH) for mRNA and U6 small nuclear RNA 1 (U6) for miRNA, using normalized relative fold changes 48 h post-immunostimulation. Protein expression was quantified 72 h post-stimulation by Western blotting. Reference-based RNA-seq of immunostimulated pSS1 and nSS2 cells was performed to characterize the reactome of genes conserved across all used doses. The expression of ETS1 and STAT1 protein was upregulated (p < 0.05) in IFN-γ-treated pSS1 and nSS2, as compared to A253 cells. IFN-γ-treated nSS2 cell showed significant IL33 upregulation. Also, IL33 had a correlated (p < 0.01) U-shaped response for low-mid-range doses for IFN-γ- and poly(I:C)-treated pSS1 cells. RNA-seq showed 175 conserved differentially expressed (DE) genes between nSS2 and pSS1 immunostimulated cells. Of these, 44 were shown to interact and 39 were more abundant (p < 0.05) in pSS1 cells. Western blotting demonstrated nSS2 cells expressing ETS1 uniformly across treatments compared to pSS1 cells, despite similar mRNA abundance. miR-145b and miR-193b were significantly under-expressed in IFN-γ-treated nSS2 cells compared to pSS1 cells (p < 0.01). ETS1 and IL33 showed disproportionate mRNA and protein abundances between immunostimulated Sjögren’s disease-derived (pSS1), and sicca-derived (nSS2) cell lines. Such differences could be explained by higher levels of miR-145b and miR-193b present in pSS1 cells. Also, RNA-seq results suggested an increased sensitivity of pSS1 cells to immunostimulation. These results reflect current pathobiology aspects, confirming the relevance of immortalized salivary gland epithelial cell lines. Full article
Show Figures

Figure 1

Back to TopTop