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Clinical and Experimental Rheumatology Dec 2023Wide variety in salivary gland 18F-FDG-uptake is observed in the general population. A general consensus about the usefulness of 18F-FDG-PET/CT to detect salivary gland...
OBJECTIVES
Wide variety in salivary gland 18F-FDG-uptake is observed in the general population. A general consensus about the usefulness of 18F-FDG-PET/CT to detect salivary gland inflammatory conditions, such as in primary Sjögren's syndrome (pSS), is not yet clear. This study aimed to investigate whether there are differences in uptake of 18F-FDG in salivary glands among two autoimmune groups [pSS, giant cell arteritis (GCA)] and a non-autoimmune group (lung cancer).
METHODS
PSS patients aged ≥50 years who underwent 18F-FDG-PET/CT were included and age-matched with GCA patients and a non-autoimmune control group (lung cancer patients). Scans were visually evaluated and quantitative analysis was performed by measuring standardised uptake values (SUV) within salivary glands and lacrimal glands. For GCA patients, arteries in the vicinity of the parotid and submandibular gland were assessed for positivity.
RESULTS
PSS patients did not show increased 18F-FDG-uptake in the parotid or submandibular gland, compared to the other two groups. For the tubarial gland, significantly higher SUVmax was found in the pSS patient group. Interestingly, GCA patients had significantly higher SUVmax in the submandibular gland than the other two groups. Visual 18F-FDG-positivity of cranial arteries related to the parotid and submandibular glands was associated with significantly higher SUVmax in salivary glands of GCA patients.
CONCLUSIONS
Although 18F-FDG-uptake was not increased in parotid and submandibular glands of pSS patients, increased 18F-FDG-uptake in tubarial glands of pSS patients might indicate a role for these glands in pSS. Furthermore, parotid and submandibular glands may be affected by local vasculitis in GCA.
Topics: Humans; Sjogren's Syndrome; Fluorodeoxyglucose F18; Positron Emission Tomography Computed Tomography; Giant Cell Arteritis; Salivary Glands; Parotid Gland; Submandibular Gland; Lung Neoplasms
PubMed: 38079331
DOI: 10.55563/clinexprheumatol/8qt9me -
Biomolecules Aug 2023The possible usefulness of alpha-synuclein (aSyn) determinations in peripheral tissues (blood cells, salivary gland biopsies, olfactory mucosa, digestive tract, skin)... (Review)
Review
The possible usefulness of alpha-synuclein (aSyn) determinations in peripheral tissues (blood cells, salivary gland biopsies, olfactory mucosa, digestive tract, skin) and in biological fluids, except for cerebrospinal fluid (serum, plasma, saliva, feces, urine), as a marker of several diseases, has been the subject of numerous publications. This narrative review summarizes data from studies trying to determine the role of total, oligomeric, and phosphorylated aSyn determinations as a marker of various diseases, especially PD and other alpha-synucleinopathies. In summary, the results of studies addressing the determinations of aSyn in its different forms in peripheral tissues (especially in platelets, skin, and digestive tract, but also salivary glands and olfactory mucosa), in combination with other potential biomarkers, could be a useful tool to discriminate PD from controls and from other causes of parkinsonisms, including synucleinopathies.
Topics: Humans; alpha-Synuclein; Nervous System Diseases; Synucleinopathies; Body Fluids; Biopsy
PubMed: 37627328
DOI: 10.3390/biom13081263 -
Otolaryngologia Polska = the Polish... Sep 2023<br><b>Introduction:</b> Malignant minor salivary gland tumors are rare, accounting for fewer than 1% of all laryngeal cancers.</br>...
<br><b>Introduction:</b> Malignant minor salivary gland tumors are rare, accounting for fewer than 1% of all laryngeal cancers.</br> <br><b>Aim:</b> This study aims to share our experiences regarding clinical, radiological, pathological profiles and their management.</br> <br><b>Materials and methods:</b> The current study reviews 11 cases of malignant minor salivary gland tumors of the larynx treated surgically at our Institute between 2005 and 2019.</br> <br><b>Results:</b> The mean age of the patients was 54 years (range 38-75 years) with six females and five males in the series (1.2:1). Subglottis and trachea were the sites of origin in 54% of the cases, and hoarseness with dyspnea were the most common presenting symptoms. There were nine Adenoid cystic and two Mucoepidermoid carcinoma patients. Surgery was the primary mode of treatment.</br> <br><b>Conclusions:</b> Most of the larynx's malignant minor salivary gland tumors are submucosal in origin. The outcome and prognosis vary considerably based on the tumor's histology, grade, and stage.</br>.
Topics: Female; Male; Humans; Adult; Middle Aged; Aged; Adenoids; Hoarseness; Laryngeal Neoplasms; Larynx; Salivary Gland Neoplasms
PubMed: 38032326
DOI: 10.5604/01.3001.0053.4040 -
Frontiers in Immunology 2023Primary Sjogren's syndrome (pSS) is a prototypical systemic autoimmune disease characterised by lymphocyte infiltration and immune-complex deposition in multiple organs....
BACKGROUND
Primary Sjogren's syndrome (pSS) is a prototypical systemic autoimmune disease characterised by lymphocyte infiltration and immune-complex deposition in multiple organs. The specific distribution of immune cell populations and their relationship with mitochondria remain unknown.
METHODS
Histological analysis was performed to assess the specific distribution of innate and adaptive immune cell populations in labial salivary gland (LSG) samples from 30 patients with pSS and 13 patients with non-pSS. The ultrastructural morphometric features of mitochondria within immune cells were observed under the transmission electron microscope (TEM). RNA sequencing was performed on LSG samples from 40 patients with pSS and 7 non-pSS patients. The Single-sample Gene Set Enrichment Analysis (ssGSEA), ESTIMATE, and CIBERSORT algorithms and Pearson correlation coefficients were used to examine the relationship between mitochondria-related genes and immune infiltration. Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify the mitochondria-specific genes and the related pathways based on the immune cell types.
RESULTS
HE staining revealed a massive infiltration of plasma cells with abundant immunoglobulin protein distributed around phenotypically normal-appearing acinar and ductal tissues of patients with pSS. Immunohistochemical analyses revealed that innate immune cells (macrophages, eosinophils and NK cells) were distributed throughout the glandular tissue. Dominant adaptive immune cell infiltration composed of B cells, CD4T cells and CD8 T cells or ectopic lymphoid follicle-like structures were observed in the LSGs of patients with pSS. TEM validated the swelling of mitochondria with disorganised cristae in some lymphocytes that had invaded the glandular tissue. Subsequently, bioinformatic analysis revealed that innate and adaptive immune cells were associated with different mitochondrial metabolism pathways. Mitochondrial electron transport and respiratory chain complexes in the glandular microenvironment were positively correlated with innate immune cells, whereas amino acid and nucleic acid metabolism were negatively correlated with adaptive immune cells. In addition, mitochondrial biogenesis and mitochondrial apoptosis in the glandular microenvironment were closely associated with adaptive immune cells.
CONCLUSION
Innate and adaptive immune cells have distinct distribution profiles in the salivary gland tissues of patients with pSS and are associated with different mitochondrial metabolic pathways, which may contribute to disease progression.
Topics: Humans; Salivary Glands; Sjogren's Syndrome; CD8-Positive T-Lymphocytes; Mitochondria; Metabolome
PubMed: 37497211
DOI: 10.3389/fimmu.2023.1156774 -
Frontiers in Immunology 2023Primary Sjogren Syndrome (pSS) is an autoimmune disease characterized by immune cell infiltration. While the presence of follicular T helper (Tfh) cells in the glandular...
BACKGROUND
Primary Sjogren Syndrome (pSS) is an autoimmune disease characterized by immune cell infiltration. While the presence of follicular T helper (Tfh) cells in the glandular microenvironment has been observed, their biological functions and clinical significance remain poorly understood.
METHODS
We enrolled a total of 106 patients with pSS and 46 patients without pSS for this study. Clinical data and labial salivary gland (LSG) biopsies were collected from all participants. Histological staining was performed to assess the distribution of Tfh cells and B cells. Transcriptome analysis using RNA-sequencing (RNA-seq) was conducted on 56 patients with pSS and 26 patients without pSS to uncover the underlying molecular mechanisms of Tfh cells. To categorize patients, we employed the single-sample gene set enrichment analysis (ssGSEA) algorithm, dividing them into low- and high-Tfh groups. We then utilized gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), and deconvolution tools to explore functional and immune infiltration differences between the low- and high-Tfh groups.
RESULTS
Patients with pSS had a higher positive rate of the antinuclear antibody (ANA), anti-Ro52, anti-SSA, anti-SSB and hypergammaglobulinaemia and higher levels of serum IgG compared to the non-pSS. Histopathologic analyses revealed the presence of Tfh cells (CD4CXCR5ICOS) in germinal centers (GC) within the labial glands of pSS patients. GSEA, WGCNA, and correlation analysis indicated that the high-Tfh group was associated with an immune response related to virus-mediated IFN response and metabolic processes, primarily characterized by hypoxia, elevated glycolysis, and oxidative phosphorylation levels. In pSS, most immune cell types exhibited significantly higher infiltration levels in the high-Tfh group compared to the low-Tfh group. Additionally, patients in the Tfh-high group demonstrated a higher positive rate of the ANA, rheumatoid factor (RF), and hypergammaglobulinaemia, as well as higher serum IgG levels.
CONCLUSION
Our study suggests that Tfh cells may play a crucial role in the pathogenesis of pSS and could serve as potential therapeutic targets in pSS patients.
Topics: Humans; Transcriptome; Hypergammaglobulinemia; Sjogren's Syndrome; Systems Biology; T Follicular Helper Cells; Antibodies, Antinuclear; Immunoglobulin G
PubMed: 37638029
DOI: 10.3389/fimmu.2023.1216379 -
Nature Communications Aug 2023Regulation of high-density loci harboring genes with different cell-specificities remains a puzzle. Here we investigate a locus that evolved through gene duplication and...
Regulation of high-density loci harboring genes with different cell-specificities remains a puzzle. Here we investigate a locus that evolved through gene duplication and contains eight genes and 20 candidate regulatory elements, including one super-enhancer. Casein genes (Csn1s1, Csn2, Csn1s2a, Csn1s2b, Csn3) are expressed in mammary glands, induced 10,000-fold during pregnancy and account for 50% of mRNAs during lactation, Prr27 and Fdcsp are salivary-specific and Odam has dual specificity. We probed the function of 12 candidate regulatory elements, individually and in combination, in the mouse genome. The super-enhancer is essential for the expression of Csn3, Csn1s2b, Odam and Fdcsp but largely dispensable for Csn1s1, Csn2 and Csn1s2a. Csn3 activation also requires its own local enhancer. Synergism between local enhancers and cytokine-responsive promoter elements facilitates activation of Csn2 during pregnancy. Our work identifies the regulatory complexity of a multigene locus with an ancestral super-enhancer active in mammary and salivary tissue and local enhancers and promoter elements unique to mammary tissue.
Topics: Female; Pregnancy; Animals; Mice; Regulatory Sequences, Nucleic Acid; Promoter Regions, Genetic; Lactation; Salivary Glands; Caseins
PubMed: 37591874
DOI: 10.1038/s41467-023-40712-0 -
Tissue Barriers Oct 2023Salivary glands consist of highly specialized epithelial cells that secrete the fluid, saliva, and/or transport saliva into the oral cavity. Saliva is essential to... (Review)
Review
Salivary glands consist of highly specialized epithelial cells that secrete the fluid, saliva, and/or transport saliva into the oral cavity. Saliva is essential to lubricate the oral cavity for food consumption and to maintain the hygiene of the oral cavity. In this review, we will focus on the formation of the epithelial cell lineage and the cell junctions that are essential for formation of saliva and maintenance of the epithelial barrier between the ducts that transport saliva and the extracellular environment.
Topics: Submandibular Gland; Tight Junctions; Salivary Glands; Epithelial Cells; Intercellular Junctions
PubMed: 36576256
DOI: 10.1080/21688370.2022.2161255 -
Cells Oct 2023Salivary gland tumors (SGTs) are rare and complex neoplasms characterized by heterogenous histology and clinical behavior as well as resistance to systemic therapy....
Salivary gland tumors (SGTs) are rare and complex neoplasms characterized by heterogenous histology and clinical behavior as well as resistance to systemic therapy. Tumor etiology is currently under elucidation and an interplay of genetic and epigenetic changes has been proposed to contribute to tumor development. In this work, we investigated epigenetic regulators and histone-modifying factors that may alter gene expression and participate in the pathogenesis of SGT neoplasms. We performed a detailed bioinformatic analysis on a publicly available RNA-seq dataset of 94 ACC tissues supplemented with clinical data and respective controls and generated a protein-protein interaction (PPI) network of chromatin and histone modification factors. A significant upregulation of and histone-modifying enzymes SUV39H1, EZH2, PRMT1, HDAC8, and KDM5B, along with the upregulation of DNA methyltransferase DNMT3A and ubiquitin ligase UHRF1 mRNA levels, as well as a downregulation of lysine acetyltransferase KAT2B levels, were detected in ACC tissues. The protein expression of p53, SUV39H1, EZH2, and HDAC8 was further validated in SGT tissues along with their functional deposition of the repressive histone marks H3K9me3 and H3K27me3, respectively. Overall, this study is the first to detect a network of interacting proteins affecting chromatin structure and histone modifications in salivary gland tumor cells, further providing mechanistic insights in the molecular profile of SGTs that confer to altered gene expression programs.
Topics: Humans; Histones; Chromatin; Methyltransferases; Epigenesis, Genetic; Salivary Gland Neoplasms; Protein-Arginine N-Methyltransferases; Repressor Proteins; CCAAT-Enhancer-Binding Proteins; Ubiquitin-Protein Ligases; Histone Deacetylases
PubMed: 37887281
DOI: 10.3390/cells12202437 -
Pharmaceutics Dec 2023Oral dryness is among the most common conditions experienced by the elderly. As saliva plays a crucial role in maintaining oral health and overall quality of life, the...
Oral dryness is among the most common conditions experienced by the elderly. As saliva plays a crucial role in maintaining oral health and overall quality of life, the condition is increasingly taking its toll on a rapidly growing aging population. D-galactose (D-gal) stimulates their formation, which in turn cause oxidative stress and accelerate age-related decline in physical function. In this study, we observed a reduction in salivary secretion and amylase levels in aged rats injected with D-gal, confirming salivary gland dysfunction. Treatment with gemigliptin increased DPP-4 inhibition and GLP-1 levels in the salivary glands of aging rats and reduced the expression of AGEs and receptors for advanced glycation end products (RAGE). This effect was caused by the presence of additional reactive oxygen species (ROS) in the salivary glands of the examined rats. Gemigliptin's cytoprotective effect reduced amylase and mucin accumulation and increased AQP5 expression, which are important indicators of salivary gland function. In sum, gemigliptin was shown to improve D-gal-induced decline in the salivary gland function of aged rats through its anti-glycation and antioxidant activities. Gemigliptin shows promise as a treatment strategy for patients experiencing decreased salivary function associated with their advancing age.
PubMed: 38258046
DOI: 10.3390/pharmaceutics16010035 -
Journal of Otolaryngology - Head & Neck... Aug 2023Juvenile recurrent parotitis (JRP) is characterized by recurrent episodes of painful parotid swelling in children. The purpose of this systematic review was to determine... (Review)
Review
BACKGROUND
Juvenile recurrent parotitis (JRP) is characterized by recurrent episodes of painful parotid swelling in children. The purpose of this systematic review was to determine the diagnostic and therapeutic effectiveness of sialendoscopy in children affected by JRP.
METHODS
A systematic literature search was performed in PubMed, EMBASE, Scopus and the Cochrane Library until April 2022, without language restrictions or specified start date. Quality assessment was performed using the Newcastle-Ottawa Scale (NOS).
RESULTS
Our review included 524 patients and 646 sialendoscopies. The sample sizes of the different studies ranged from 3 to 77 subjects. Most authors performed sialendoscopy under general anesthesia. The mean percentage of recurrences observed was 25.1% (95% confidence intervals) (CI 23.6-26.6). There was a statistically significant relationship between the number of attacks/year and recurrences (p < 0.05). The percentage of recurrences according to the type of irrigation/flushing used ranged from 22.2% to 25.2%, with no significant differences between the use of corticosteroids alone (25.2% of recurrences), corticosteroids plus antibiotics (25% of recurrences) or saline alone (22.2% of recurrences). Sialoendoscopy has proved in all cases to be a valid method for the diagnosis of JRP, but it does not allow a reliable differential diagnosis with other autoimmune parotitis such as Sjögren's syndrome.
CONCLUSION
According to our results, parotid sialoendoscopy was 74.9% effective as a primary treatment in the prevention of recurrent symptoms in JRP. The type of ductal irrigation used did not significantly influence the prognostic outcome.
Topics: Child; Humans; Parotitis; Parotid Gland; Anesthesia, General; Recurrence
PubMed: 37598195
DOI: 10.1186/s40463-023-00658-1