Search Results (909)

Sjögren’s syndrome (SS) is an autoimmune disease characterized by heterogeneous clinical presentation and the presence of various autoantibodies. This study aimed to determine the differences in clinical findings according to antibody positivity in patients with primary Sjögren syndrome (pSS) in the Turkish population. A retrospective study was conducted and 402 patients (378 women and 24 men) with pSS were analyzed. The patients were categorized into three subgroups based on serological tests. These were (1) quadruple seropositivity (positive for anti-Sjögren’s syndrome-related antigen A antibodies (anti-SSA; anti-Ro) and anti-Sjögren’s syndrome-related antigen B antibodies (anti-SSB; anti-La), rheumatoid factor (RF), and antinuclear antibody (ANA); (2) double seropositivity (positive for ANA and anti-SSA/Ro antibodies); and (3) quadruple seronegativity (negative for ANA, RF, anti-SSA/Ro and anti-SSB/La antibodies). The number of quadruple-seropositive patients was 72 (18.6%), double-seropositive 174 (43.2%), and quadruple-seronegative was 85 (21.1%). The age at diagnosis of quadruple-seropositive pSS was 42.4 ± 10.8, which was significantly younger than that of patients with double-seropositive and quadruple-seronegative pSS (p = 0.021, p = 0.112). In terms of organ involvement, salivary gland enlargement, arthralgia, arthritis, Raynaud’s phenomenon, lymphadenopathy, cutaneous vasculitis, interstitial lung disease, neurological involvement, autoimmune thyroiditis, renal interstitial disease, anemia, leukopenia, hypergammaglobulinemia, and hypocomplementemia were more common in quadruple-seropositive patients with pSS than in quadruple-seronegative patients (p < 0.0001). The results of this study confirmed the strong impact of immunological markers on the pSS phenotype at the time of diagnosis. Immunological patterns play a central role in the phenotypic expression of the disease, even during the initial diagnostic phase, and can guide physicians in designing personalized treatment plans for patients with pSS. Full article

Purpose: To investigate the impact of physiologically based pharmacokinetic (PBPK) parameters on physical, biological, and statistical measures in lutetium-177-labeled radiopharmaceutical therapies (RPTs) targeting the prostate-specific membrane antigen (PSMA). Methods: Using a clinically validated PBPK model, realistic time–activity curves (TACs) for tumors, salivary glands, and kidneys were generated based on various model parameters. These TACs were used to calculate the area-under-the-TAC (AUC), dose, biologically effective dose (BED), and figure-of-merit BED (fBED). The effects of these parameters on radiobiological, pharmacokinetic, time, and statistical features were assessed. Results: Manipulating PBPK parameters significantly influenced AUC, dose, BED, and fBED outcomes across four different BED models. Higher association rates increased AUC, dose, and BED values for tumors, with minimal impact on non-target organs. Increased internalization rates reduced AUC and dose for tumors and kidneys. Higher serum protein-binding rates decreased AUC and dose for all tissues. Elevated tumor receptor density and ligand amounts enhanced uptake and effectiveness in tumors. Larger tumor volumes required dosimetry adjustments to maintain efficacy. Setting the tumor release rate to zero intensified the impact of association and internalization rates, enhancing tumor targeting while minimizing the effects on salivary glands and kidneys. Conclusions: Optimizing PBPK parameters can enhance the efficacy of lutetium-177-labeled RPTs targeting PSMA, providing insights for personalized and effective treatment regimens to minimize toxicity and improve therapeutic outcomes. Full article

The process of stone formation in the human body remains incompletely understood, which requires clinical and laboratory studies and the formulation of a new endogenous, nanotechnological concept of the mechanism of origin and formation of crystallization centers. Previously, the mechanism of sialolithiasis was considered a congenital disease associated with the pathology of the ducts in the structure of the glands themselves. To date, such morphological changes of congenital nature can be considered from the position of the intrauterine formation of endogenous bacterial infections complicated by the migration of antigenic structures initiating the formation of crystallization centers. The present work is devoted to the study of the morphology and composition of stones obtained as a result of surgical interventions for sialolithiasis. Presumably, nanoparticles of metals and other chemical compounds can be structural components of crystallization centers or incorporated into the conditions of chronic endogenous inflammation and the composition of antigenic structures, in complexes with protein and bacterial components. X-ray microtomography, X-ray fluorescence analysis, scanning transmission electron microscopy and microanalysis, mass spectrometry, and Raman spectroscopy were used to study the pathogenesis of stone formation. Immunoglobulins (Igs) of classes A and G, as well as nanoparticles of metals Pb, Fe, Cr, and Mo, were found in the internal structure of the stones. The complex of antigenic structures was an ovoid calcified layered matrix of polyvid microbial biofilms, with the inclusion of metal nanoparticles and chemical elements, as well as immunoglobulins. The obtained results of clinical and laboratory studies allow us to broaden the view on the pathogenesis of stone formation and suggest that the occurrence of the calcification of antigenic structures may be associated with the formation of IgG4-associated disease. Full article

Salivary gland tumors are a rare and heterogeneous group of neoplasms of the head and neck region. The mixed category of these tumors include the following entities: pleomorphic adenoma (PA), carcinoma ex pleomorphic adenoma (CEPA), salivary carcinosarcoma (CS), and metastasizing PA (MPA). The most common benign tumor of the salivary glands is PA. Metastasis and malignant degeneration have been reported in cases of PA of a salivary gland origin. Judging by their behavior, MPA, CEPA, and CS can be considered aggressive tumors. Invasive CEPA has been identified in the parotid gland more frequently. MPA and CS cases reported in the current literature are rare. In this paper, we present, narratively, the clinico-morphological features of this group of mixed tumors. Full article

Energy drink (ED) consumption has become increasingly popular. Due to a lack of evidence, it was crucial to assess the effects of Red Bull (RB) consumption on the rat submandibular salivary gland and the potential therapeutic impact of blueberry (BB). Thirty rats were randomly assigned to five groups. Group 1 (Control) received distilled water. Group 2 (RB) received RB (10 mL/100 g/day) for 8 weeks. Group 3 (BB) rats were administered BB (500 mg/day for 8 weeks). Group 4 (RB + BB (L)) received RB for 8 weeks, and from the 5th week, were concurrently given BB (250 mg/day) for 4 weeks. Group 5 (RB + BB (H)) received RB for 8 weeks, and from the 5th week, were concurrently given BB (500 mg/day) for 4 weeks. At the end of the experiment, blood samples were collected, the animals were euthanized, and their submandibular salivary glands were harvested. Oxidative stress markers (MDA, GPx, CAT, and SOD) were assessed in both serum and tissue. Inflammatory markers (TNF-α, IL-6, and IL-10) were quantified in tissue. Submandibular gland specimens were prepared for light microscopy, and immunohistochemical staining was performed using anti-α-SMA. RB consumption resulted in a significant increase in MDA, TNF-α, IL-6, and IL-10, while GPx, CAT, and SOD levels decreased significantly. Degenerative changes in the gland’s structure were observed in the RB group. A significant increase in α-SMA immunoreaction was detected in myoepithelial cells. Administration of BB, particularly at a high dose, ameliorated the aforementioned findings. In conclusion, blueberry administration exhibited therapeutic effects due to its antioxidative and anti-inflammatory properties. Full article

Ceresini treehoppers are present in northern California vineyard ecosystems, including the closely related Spissistilus and Tortistilus (Hemiptera: Membracidae). These membracids are not direct pests of wine grapes, but S. festinus is a vector of grapevine red blotch virus (GRBV). No information is available on the ability of Tortistilus spp. to transmit GRBV. In this study, Tortistilus were collected on yellow panel cards across 102 vineyard sites and surrounding areas in Napa Valley, California, USA in 2021–2023. Specimens were morphotyped, sexed and tested for GRBV ingestion and acquisition by multiplex PCR or qPCR. Phylogenetic analysis of the partial sequence of mt-COI and ITS gene fragments of a subset of 40 Tortistilus specimens revealed clustering in a monophyletic clade with T. wickhami with the former barcode sequence. Only 6% (48/758) of the T. wickhami tested positive for GRBV, but none of the heads with salivary glands (0%, 0/50) of the dissected specimens tested positive for GRBV, indicating no virus acquisition. In contrast, half of the dissected heads with salivary glands of S. festinus (52%, 12/23), from the same collection vineyard sites, tested positive for GRBV. Together, our findings confirmed the presence of T. wickhami in northern California vineyards and suggested a dubious role of this treehopper as a vector of GRBV. Full article

Xerostomia induced by antidepressants such as imipramine has long been thought to be due to their anticholinergic effects. However, even antidepressants with low anticholinergic effects may have a high incidence of xerostomia. In salivary glands, norepinephrine activates alpha-adrenergic receptors in blood vessels and beta-adrenergic receptors in acinar cells, respectively, causing a decrease in the blood flow and an increase in the protein secretion, resulting in the secretion of viscous saliva with low water content and high protein content. A previous study demonstrated that perfusion of the submandibular glands of rats with serotonin significantly decreased saliva secretion. The results of the present study revealed the following: (1) that norepinephrine and serotonin, but not epinephrine nor dopamine, were detected in the interstitial fluids in rat submandibular glands; (2) that norepinephrine and serotonin concentrations in the dialysate was 4.3 ± 2.8 nM and 32.3 ± 19.6 nM at stable level, respectively; (3) that infusion with imipramine, a reuptake inhibitor of norepinephrine and serotonin, significantly and dose-dependently increased both norepinephrine and serotonin concentrations in the dialysate; and (4) that intraperitoneal administration of imipramine significantly increased both norepinephrine and serotonin concentrations in the dialysate. These results suggested that one of the mechanisms of xerostomia induced by reuptake inhibitors of norepinephrine and serotonin involves the activation of adrenergic and serotonin receptors in the salivary glands, respectively. Full article

Salivary gland cancer (SGC) is a rare cancer that can present a diagnostic challenge to pathologists, with emerging, but still limited options for the treatment of recurrent/metastatic disease. We aimed to characterize the cohort of salivary gland cancers in our institute and generate a tissue microarray (TMA) with clinical data available for immunohistochemical analysis. We extracted the cases of salivary gland cancers in our institute and generated a TMA with 72 patients between 2002 and 2017 with sufficient paraffin block material. Follow-up data were present for all cases. The TMA was stained with three p53 antibodies as well as MSH2, MSH6, PMS2 and MLH1 antibodies. Additionally, we applied fragment analysis based on the Bethesda panel, and the IdyllaTM MSI test to cases with expression loss of any of the mismatch repair proteins (MMR-P) according to our immunohistochemistry (IHC). The investigated cohort shows that pT and pN stage are the only factors independently associated with survival, according to our multivariate analysis (p = 0.037 and p = 0.014). In univariate analysis, risk factors identified in our cohort were also age (p = 0.015), (lympho-) vascular invasion (p = 0.002 and p = 0.003) and risk stratification (p = 0.037). The p53 protein investigated by three antibodies showed no statistically significant association with survival or other tumor characteristics in the investigated cohort. According to MMR-P IHC, six cases of SGC showed an aberrant IHC phenotype. Additional IdyllaTM MSI test and fragment length analysis failed to confirm microsatellite instability. The pT and pN stage are the most important factors for survival in our cohort. In our cohort, antibodies directed against the protein p53 did not contribute to clinical decision-making and were not correlated with any known clinical characteristics. MSI appears to be insignificant in SGCs. Larger cohorts are needed for verification. Full article

In Sjögren’s disease (SjD), the salivary glandular epithelial cells can induce the chemotaxis of B cells by secreting B-cell chemokines such as C-X-C motif chemokine ligand 13 (CXCL13). Syndecan-1 (SDC-1) is a major transmembrane heparan sulfate proteoglycan (HSPG) predominantly expressed on epithelial cells that binds to and regulates heparan sulfate (HS)-binding molecules, including chemokines. We aimed to determine whether SDC-1 plays a role in the pathogenesis of SjD by acting on the binding of HS to B-cell chemokines. To assess changes in glandular inflammation and SDC-1 concentrations in the submandibular gland (SMG) and blood, female NOD/ShiLtJ and sex- and age-matched C57BL/10 mice were used. In the SMG of NOD/ShiLtJ mice, inflammatory responses were identified at 8 weeks of age, but increased SDC-1 concentrations in the SMG and blood were observed at 6 weeks of age, when inflammation had not yet started. As the inflammation of the SMG worsened, the SDC-1 concentrations in the SMG and blood increased. The expression of the CXCL13 and its receptor C-X-C chemokine receptor type 5 (CXCR5) began to increase in the SMG at 6 weeks of age and continued until 12 weeks of age. Immunofluorescence staining in SMG tissue and normal murine mammary gland cells confirmed the co-localization of SDC-1 and CXCL13, and SDC-1 formed a complex with CXCL13 in an immunoprecipitation assay. Furthermore, NOD/ShiLtJ mice were treated with 5 mg/kg HS intraperitoneally thrice per week for 6–10 weeks of age, and the therapeutic effects in the SMG were assessed at the end of 10 weeks of age. NOD/ShiLtJ mice treated with HS showed attenuated salivary gland inflammation with reduced B-cell infiltration, germinal center formation and CXCR5 expression. These findings suggest that SDC-1 plays a pivotal role in the pathogenesis of SjD by binding to CXCL13 through the HS chain. Full article

Primary Sjogren’s syndrome (pSS) is often concomitant with fibromyalgia (FM). Salivary gland sonography aids in the diagnosis of pSS. We aimed to discover, in primary FM patients, the presence of pSS in undiagnosed patients through salivary gland sonography. We prospectively recruited 42 primary FM patients. FM symptoms were evaluated based on the revised Fibromyalgia Impact Questionnaire (FIQR). Salivary gland sonography was performed. Patients with positive findings underwent salivary gland biopsy. Comparisons were undertaken using the Mann–Whitney U tests and Chi-squared test. In primary FM patients, the prevalence of dry eye was 83%, and dry mouth was 90%. The salivary gland sonographic score did not differ between patients with and without dry eye/mouth. One patient with a positive finding at salivary gland sonography had a positive result of salivary gland biopsy. In the other four patients who received salivary gland biopsy, despite negative findings in salivary gland sonography, only one had a positive result of salivary gland biopsy. To be noted, scores evaluated by salivary gland sonography were negatively associated with levels of pain (rho = −0.360, p= 0.023) and levels of sleep quality (rho = −0.447, p = 0.004). Our pilot study demonstrated the potential of salivary gland biopsy in detecting undiagnosed pSS in primary FM patients. Full article

Background: Metastatic tumors of the oro-facial tissuesare rare, with an incidence ranging between 1% and 8% of all oral malignant tumors. Generally reported with a peak of incidence in the 5–7th decades but possibly occurring at any age, metastases may represent the first sign of an occult cancer or manifest in patients with an already known history of a primary carcinoma, mostly from the lungs, kidney, prostate, and colon/rectum in males, and the uterus, breast, lung, and ovary in females. In the oro-facial tissues, the most involved sites are the oral mucosa, gingiva/jawbones, tongue, and salivary glands. Methods: A broad and deep literature review with a comprehensive analysis of the existing research on oro-facial metastases from renal-cell carcinoma (RCC) was conducted by searching the most used databases, with attention also paid to the clear-cell histological variant, which is the most frequent one. Results: Among the 156 analyzed studies, 206 cases of oro-facial metastases of renal cancer were found in patients with an average age of 60.9 years (145 males, 70.3%; 61 females, 29.6%). In almost 40% of the cases, metastasis represented the first clinical manifestation of the primary tumor, and 122 were histologically diagnosed as clear-cell renal-cell carcinoma (ccRCC) (59.2%). The tongue was involved in most of the cases (55 cases, 26.7%), followed by the gingiva (39 cases, 18.9%), mandible (35 cases, 16.9%), maxilla (23 cases, 11.1%), parotid gland (22 cases, 10.6%), buccal mucosa (11 cases, 5.3%), lips (7 cases, 3.3%), hard palate (6 cases, 2.8%), soft palate, masticatory space, and submandibular gland (2 cases, 0.9%), and lymph nodes, tonsils, and floor of the mouth (1 case, 0.4%). Among the 122 ccRCCs (84 males, 68.8%; 38 females, 31.1%), with an average age of 60.8 years and representing in 33.6% the first clinical manifestation, the tongue remained the most frequent site (31 cases, 25.4%), followed by the gingiva (21 cases, 17.2%), parotid gland (16 cases, 13.1%), mandibular bone (15 cases, 12.2%), maxillary bone (14 cases, 11.4%), buccal mucosa and lips (6 cases, 4.9%), hard palate (5 cases, 4%), submandibular gland and soft palate (2 cases, 1.6%), and lymph nodes, tonsils, oral floor, and masticatory space (1 case, 0.8%). The clinical presentation in soft tissues was mainly represented by a fast-growing exophytic mass, sometimes accompanied by pain, while in bone, it generally presented as radiolucent lesions with ill-defined borders and cortical erosion. Conclusions: The current comprehensive review collected data from the literature about the incidence, site of occurrence, age, sex, and survival of patients affected by oro-facial metastases from renal-cell carcinoma, with particular attention paid to the cases diagnosed as metastases from clear-cell renal-cell carcinoma, which is the most frequent histological variant. Clinical differential diagnosis is widely discussed to provide clinicians with all the useful information for an early diagnosis despite the effective difficulties in recognizing such rare and easily misdiagnosed lesionsTheir early identification represents a diagnostic challenge, especially when the clinical work-up is limited to the cervico–facial region. Nevertheless, early diagnosis and recently introduced adjuvant therapies may represent the key to better outcomes in such patients. Therefore, general guidelines about the clinical and radiological identification of oro-facial potentially malignant lesions should be part of the cultural background of any dentist. Full article

Adenoid cystic carcinoma (ACC) of head and neck origin is associated with slow but relentless progression and systemic metastasis, resulting in poor long-term survival rates. ACC does not respond to conventional chemotherapy. Determination of molecular drivers may provide a rational basis for personalized therapy. Herein, we investigate the clinical and detailed molecular genomic features of a cohort of patients treated in Ireland and correlate the site of origin, molecular features, and outcomes. Clinical and genomic landscapes of all patients diagnosed with ACC over a twenty-year period (2002–2022) in a single unit in Ireland were examined and analyzed using fluorescence in situ hybridization, DNA sequencing, and bioinformatic analysis. Fourteen patients were included for analysis. Eleven patients had primary salivary gland ACC and three primary lacrimal gland ACC; 76.9% of the analyzed tumors displayed evidence of NFIB-MYB rearrangement at the 6q23.3 locus; 35% had mutations in NOTCH pathway genes; 7% of patients had a NOTCH1 mutation, 14.3% NOTCH2 mutation, and 14.3% NOTCH3 mutation. The presence of epigenetic modifications in ACC patients significantly correlated with worse overall survival. Our study identifies genetic mutations and signaling pathways that drive ACC pathogenesis, representing potential molecular and therapeutic targets. Full article

Background: Objective quantitative texture characteristics may be helpful in salivary glandular tumor differential diagnosis. This study uses machine learning (ML) to explore and validate the performance of ultrasound (US) texture features in diagnosing salivary glandular tumors. Material and methods: 122 patients with salivary glandular tumors, including 71 benign and 51 malignant tumors, are enrolled. Representative brightness mode US pictures are selected for further Gray Level Co-occurrence Matrix (GLCM) texture analysis. We use a t-test to test the significance and use the receiver operating characteristic curve method to find the optimal cut-point for these significant features. After splitting 80% of the data into a training set and 20% data into a testing set, we use five machine learning models, k-nearest Neighbors (kNN), Naïve Bayes, Logistic regression, Artificial Neural Networks (ANNs) and supportive vector machine (SVM), to explore and validate the performance of US GLCM texture features in diagnosing salivary glandular tumors. Results: This study includes 49 female and 73 male patients, with a mean age of 53 years old, ranging from 21 to 93. We find that six GLCM texture features (contrast, inverse difference movement, entropy, dissimilarity, inverse difference and difference entropy) are significantly different between benign and malignant tumors (p < 0.05). In ML, the overall accuracy rates are 74.3% (95%CI: 59.8–88.8%), 94.3% (86.6–100%), 72% (54–89%), 84% (69.5–97.3%) and 73.5% (58.7–88.4%) for kNN, Naïve Bayes, Logistic regression, a one-node ANN and SVM, respectively. Conclusions: US texture analysis with ML has potential as an objective and valuable tool to make a differential diagnosis between benign and malignant salivary gland tumors. Full article

Salivary gland tumors are highly variable in clinical presentation and histology. The World Health Organization (WHO) classifies 22 types of malignant and 11 types of benign tumors of the salivary glands. Diagnosis of salivary gland tumors is based on imaging (ultrasound, magnetic resonance imaging) and fine-needle aspiration biopsy, but the final diagnosis is based on histopathological examination of the removed tumor tissue. In this pilot study, we are testing a new approach to identifying peptide biomarkers in saliva that can be used to diagnose salivary gland tumors. The research material for the peptidomic studies was extracts from washings of neoplastic tissues and healthy tissues (control samples). At the same time, saliva samples from patients and healthy individuals were analyzed. The comparison of the peptidome composition of tissue extracts and saliva samples may allow the identification of potential peptide markers of salivary gland tumors in patients’ saliva. The peptidome compositions extracted from 18 tumor and 18 healthy tissue samples, patients’ saliva samples (11 samples), and healthy saliva samples (8 samples) were analyzed by LC-MS tandem mass spectrometry. A group of 109 peptides was identified that were present only in the tumor tissue extracts and in the patients’ saliva samples. Some of the identified peptides were derived from proteins previously suggested as potential biomarkers of salivary gland tumors (ANXA1, BPIFA2, FGB, GAPDH, HSPB1, IGHG1, VIM) or tumors of other tissues or organs (SERPINA1, APOA2, CSTB, GSTP1, S100A8, S100A9, TPI1). Unfortunately, none of the identified peptides were present in all samples analyzed. This may be due to the high heterogeneity of this type of cancer. The surprising result was that extracts from tumor tissue did not contain peptides derived from salivary gland-specific proteins (STATH, SMR3B, HTN1, HTN3). These results could suggest that the developing tumor suppresses the production of proteins that are essential components of saliva. Full article

Venomous marine gastropods of the superfamily Conoidea possess a rich arsenal of toxins, including neuroactive toxins. Venom adaptations might have played a fundamental role in the radiation of conoideans; nevertheless, there is still no knowledge about the venom of the most diversified family of the group: Raphitomidae Bellardi, 1875. In this study, transcriptomes were produced from the carcase, salivary glands, and proximal and distal venom ducts of the northeastern Atlantic species Raphitoma purpurea (Montagu, 1803). Using a gut barcoding approach, we were also able to report, for the first time, molecular evidence of a vermivorous diet for the genus. Transcriptomic analyses revealed over a hundred putative venom components (PVC), including 69 neurotoxins. Twenty novel toxin families, including some with high levels of expansion, were discovered. No significant difference was observed between the distal and proximal venom duct secretions. Peptides related to cone snail toxins (Cerm06, Pgam02, and turritoxin) and other venom-related proteins (disulfide isomerase and elevenin) were retrieved from the salivary glands. These salivary venom components may constitute ancestral adaptations for venom production in conoideans. Although often neglected, salivary gland secretions are of extreme importance for understanding the evolutionary history of conoidean venom. Full article