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Open research questions in Salivary Gland Disorders and Functions

360 gap statements mined from Salivary Gland Disorders and Functions papers in our 7.9M-paper local library, which holds 2,047 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • The precise cellular sources of nitric oxide in human glandular tissues remain insufficiently characterized. Prior studies have not provided ultrastructural evidence of nNOS in human salivary glands.

    Neuronal nitric oxide synthase expression in secretory cells of the human parotid and submandibular salivary glands: evidence from light and electron microscopy · 2026 · DOI

  • The clinical and serologic spectrum of sicca syndrome is not clearly defined. There is a need to identify factors associated with extraglandular manifestations.

    Clinical and serologic features of sicca syndrome in a tertiary care cohort in China: a retrospective rheumatologic study · 2026 · DOI

  • It highlights the need for effective therapies that can target the underlying mechanisms of the disease. The paper notes the challenge of validating findings using primary cells or in vivo models, as current discoveries are based on immortalized cells with limited physiological relevance.

    Programmed cell death in primary Sjögren’s disease: regulatory network analysis and therapeutic prospects evaluation · 2026 · DOI

  • However, to date, the causes of reduced salivary secretion in patients with DM2 remain unclear.

    Increased inflammation, disturbed extracellular matrix remodeling and reduced parotid and submandibular salivary gland function in male Wistar rats with type 2 diabetes · 2026 · DOI

  • However, the mechanisms linking age and disease progression remain poorly understood.

    Tissue‐Specific Expansion of Age‐Associated B Cells via IFN‐γ and IL‐21 Within Salivary Glands in Sjögren Disease · 2026 · DOI

  • Age‐associated B cells (ABCs), a subset of B cells that increase with age, have been implicated in autoimmune responses, but their role in SjD pathogenesis has not been fully clarified.

    Tissue‐Specific Expansion of Age‐Associated B Cells via IFN‐γ and IL‐21 Within Salivary Glands in Sjögren Disease · 2026 · DOI

  • Sjogren's disease (SjD) shows a strong female predominance, but the contribution of age-related hormone changes to this sex bias remains uncertain.

    Hormonal transitions across the lifespan shape susceptibility to Sjogren’s disease · 2026 · DOI

  • Antibodies targeting high-density lipoprotein (HDL) have emerged as modulators of lipid dysfunction and inflammation in several rheumatic diseases, but their relevance in SjD remains unexplored.

    Humoral responses against high-density lipoprotein are linked to unfavourable lipid and proteomic signatures in primary Sjögren’s disease—a multi-platform approach · 2026 · DOI

  • Compositional changes in circulating RF clones may warrant further investigation in larger, independent cohorts to assess their potential value as a predictive biomarker for lymphoma.

    A specific molecular profiling of secreted rheumatoid factors in Sjögren’s disease patients with lymphoma · 2026 · DOI

  • The strong female sex bias in Sjögren's disease (SjD) remains poorly understood.

    Hormonal risk factors and androgen and glucocorticoid dysregulation in Sjogren’s disease and non-Sjogren’s sicca · 2025 · DOI

  • The role of androgens in modulating salivary gland inflammation should be further investigated.

    Hormonal risk factors and androgen and glucocorticoid dysregulation in Sjogren’s disease and non-Sjogren’s sicca · 2025 · DOI

  • Although these proteins are expressed in oral-related tissues, their expression patterns and modulatory mechanisms in the salivary glands remain unknown.

    Involvement of metformin and aging in salivary expression of ACE2 and TMPRSS2 · 2025 · DOI

  • 2% There is currently insufficient evidence to routinely recommend lacrimal gland biopsy in SD (1, C) SOA 98.

    Executive summary: British Society for Rheumatology guideline on management of adult and juvenile onset Sjögren disease · 2024 · DOI

  • USS of the salivary glands can provide useful additional information to support either the presence of or lack of evidence for SD (1, A) SOA 95.

    Executive summary: British Society for Rheumatology guideline on management of adult and juvenile onset Sjögren disease · 2024 · DOI

  • There is a need to evaluate the diagnostic accuracy and clinical utility of salivary biomarkers for oral squamous cell carcinoma. Previous studies were limited to specific biomarker types, and there is a need for a comprehensive evaluation of the diagnostic landscape for salivary biomarkers.

    Diagnostic Accuracy and Clinical Utility of Salivary Biomarkers in Oral Squamous Cell Carcinoma: A Meta-Analysis · 2026 · DOI

  • Although anti-CENP-B antibodies are traditionally recognized as serological markers of SSc and PBC, their clinical significance in pSjD remains incompletely understood.

    Anti-centromere protein B antibody positivity in primary Sjögren’s disease: clinical features and prognostic implications · 2026 · DOI

  • Studies with larger sample sizes and control groups are warranted to better define responder profiles and further explore these findings. Despite the exploratory nature of this study and the inability to establish efficacy, piperine may represent a promising therapeutic option for some patients with BMS, warranting further investigation.

    Topical Piperine for the Management of Burning Mouth Syndrome: A Case Series · 2026 · DOI

  • Although this hypothesis remains speculative, it provides a plausible additional mechanism that warrants further investigation in future controlled studies. To date, clinical studies on piperine for the management of BMS and neuropathic pain are lacking.

    Topical Piperine for the Management of Burning Mouth Syndrome: A Case Series · 2026 · DOI

  • For patients with multiple sialolithiasis, few data are available regarding the treatment approaches and outcomes with gland-preserving therapies.

    Treatment Strategies and Outcome in Minimally Invasive, Gland‐Preserving Treatment for Multiple Sialolithiasis · 2026 · DOI

  • Despite extensive studies, no single cause and treatment have been determined for burning mouth syndrome. Most researchers agree that there is a central and/or peripheral neuropathic underlying disturbance in BMS patients, however psychological component in these patients is also very present.

    ANXIETY AND DEPRESSION SCORES IN PATIENTS WITH BURNING MOUTH SYNDROME · 2108 · DOI

  • Evidence for BMS treatments is often extrapolated from chronic pain literature rather than derived directly from BMS populations, limiting directness of applicability.

    Burning Mouth Syndrome 2026: From “Diagnosis of Exclusion” to a Structured Diagnostic Algorithm (Narrative Review) · 2026 · DOI

  • Further studies to confirm the inference that duct cell differences may reflect their association with different secretory elements - Exploring the therapeutic potential of modulating NO production through specific NOS inhibitors in salivary glands - Investigating the functions of NO in oral…

    Neuronal nitric oxide synthase expression in secretory cells of the human parotid and submandibular salivary glands: evidence from light and electron microscopy · 2026 · DOI

  • The sample size and population heterogeneity still need to be verified in a larger cohort, - The observation is based on immortalized HSGE cells, which have limited physiological relevance, - The findings are based on patient tissue samples and require validation using primary cells or in vivo…

    Programmed cell death in primary Sjögren’s disease: regulatory network analysis and therapeutic prospects evaluation · 2026 · DOI

  • The dataset size was limited to 480 sample images, - The class distribution was slightly imbalanced across the eight classes, - Data augmentation was necessary to mitigate the class…

    A Unified YOLOv8 Approach for Point-of-Care Diagnostics of Salivary α-Amylase · 2025 · DOI

  • Extreme heterogeneity was observed for both primary diagnostic indices, - Limited to specific biomarker types in previous meta-analyses, - Study quality was assessed using QUADAS-2, - Potential publication bias was examined using Deeks' funnel plot asymmetry…

    Diagnostic Accuracy and Clinical Utility of Salivary Biomarkers in Oral Squamous Cell Carcinoma: A Meta-Analysis · 2026 · DOI

Most-cited papers in Salivary Gland Disorders and Functions

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Open questions raised by papers listed on this page include: (1) The precise cellular sources of nitric oxide in human glandular tissues remain insufficiently characterized (“Neuronal nitric oxide synthase expression in secretory cells of the human…”, 2026); (2) There is a need to identify factors associated with extraglandular manifestations (“Clinical and serologic features of sicca syndrome in a tertiary care cohort in…”, 2026); (3) To date, the causes of reduced salivary secretion in patients with DM2 remain unclear (“Increased inflammation, disturbed extracellular matrix remodeling and reduced…”, 2026); (4) The mechanisms linking age and disease progression remain poorly understood (“Tissue‐Specific Expansion of Age‐Associated B Cells via IFN‐γ and IL‐21 Within…”, 2026); (5) Antibodies targeting high-density lipoprotein (HDL) have emerged as modulators of lipid dysfunction and inflammation in several rheumatic diseases, but their relevance in SjD remains unexplored (“Humoral responses against high-density lipoprotein are linked to unfavourable…”, 2026). 360 gap statements have been mined from Salivary Gland Disorders and Functions papers in our 7.9M-paper local library, which holds 2,047 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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