Search Results (1,114)

Background: Advanced glycation end-products (AGEs) are formed and deposited in tissues, contributing to various disorders, including diabetes, other metabolic diseases, and aging. A new epitope, AGE10, was identified in human and animal tissues using a monoclonal antibody raised against synthetic melibiose-derived glycation end-products (MAGE), which were synthesized under anhydrous conditions with bovine serum albumin or myoglobin. The biology of the AGE10 epitope, particularly its role in diseases and in cancer tissues, is not well understood. Methods: The study was aimed at investigating the immunohistochemical recognition of AGE10 with the MoAb-anti-MAGE antibody. Results: Data obtained show that AGE10 is recognized in striated muscles but not in tumors of muscular origin. AGE10 is also stained in both normal and cancerous salivary glands and in adenomas of the large intestine. The staining is cytoplasmic. Discussion: Our approach may provide a methodology for cell biology research; AGE10 may be related to an advanced lipoxidation end-product; further investigation of MAGE may clarify disease mechanisms, support the development of novel therapeutic strategies. Conclusions: The key finding is that antibodies recognize mainly the epitope in epithelial and some mesenchymal tissues. Thus, the potential for AGE10 as a diagnostic marker is limited. The implications concern the biology of this epitope, the unique tissue distribution, and a role in cellular metabolism. Full article

Malaria remains a major global health burden, and the emergence of resistance to blood stage antimalarials underscores the need for new interventions targeting earlier stages of the parasite’s life cycle. The pre-erythrocytic liver stage represents a critical bottleneck and an attractive target for chemotherapeutic and prophylactic interventions. In this study, we functionally characterized the putative E3 ubiquitin ligase Trophozoite Exported Protein 1 (TEX1; PBANKA_0102200) in Plasmodium berghei using gene knockout, tagging, and imaging approaches across the mosquito and liver stages. TEX1 knockout parasites (PbTEX1-KO) showed impaired development during mosquito-stage transitions, with significant reductions in ookinete formation, oocyst numbers, and sporozoites reaching the salivary glands. In hepatic stages, TEX1-KO parasites displayed reduced growth, abnormal nuclear division, and impaired liver stage maturation, ultimately leading to a dramatic decline in detached cell formation and blood stage infectivity. Endogenous C-terminal tagging of TEX1 with GFP and 3×HA revealed a discrete subnuclear localization pattern, indicating a critical role in DNA synthesis and/or mitotic regulation. Our findings reveal that TEX1 is required for nuclear replication and division and successful development in both the mosquito and liver stages of Plasmodium. Given its pivotal role and nuclear localization during hepatic schizogony, TEX1 represents a promising target for the development of liver stage antimalarial interventions. Full article

Objective: Pleomorphic Adenoma (PA) is the most common benign salivary gland tumor. The need and duration of follow-up post resection is debatable. The aim of our study was to examine the need for routine follow-up after PA resection. Methods: Retrospective case-series analysis of adult patients with PA, between 1990 and 2023. Numbers of office examinations, imaging studies, time from first surgery to recurrence and recurrence detection modality were collected. Results: Overall, 301 patients had undergone surgery for PA, of which 28 experienced recurrence (9.3%). Mean time from surgery to first recurrence was 119.5 months (range, 33–274). Of the 40 recurrences, 36 were self-discovered (90%), 2 by clinical examination (5%) and 2 by imaging (5%). A total of 618 office examinations and 155 imaging studies were performed. Conclusions: Routine examinations and imaging appear to be of low yield in most PA patients, specifically in the first 3 years. Patients should be counseled about self-detection and ominous symptoms necessitating evaluation. Full article

Recurrent canine cervical sialocele is most often caused by incomplete excision of the mandibular–sublingual gland complex, leading to anatomical distortion and concealment of residual tissue. This case describes the multimodal management of a repeatedly recurrent cervical sialocele in a young, small-breed dog following multiple previous revision surgeries. A stepwise bridging strategy was adopted before definitive salvage surgery. Oral phenobarbital was instituted, resulting in partial reduction in fluid accumulation and improved comfort. Ultrasound-guided intracavitary sclerotherapy with OK-432 was then performed, inducing a localized fibrotic response but without durable cure. Final resolution was achieved only after salvage ventral paramedian (VPM) sialoadenectomy, which provided wide exposure for complete excision of deeply concealed sublingual remnant tissue within a fibrotic pseudocapsule. Histology confirmed a cervical sialocele. Transient neuropraxia resolved within 3 weeks, and no recurrence was observed at 6 months postoperatively. To the authors’ knowledge, this is the first report describing intracavitary OK-432 sclerotherapy as part of a staged multimodal strategy for canine cervical sialocele. This case illustrates the feasibility of integrating medical salivary suppression and minimally invasive sclerotherapy as bridging measures before salvage VPM surgery for refractory cervical sialocele. Full article

Survival rates for children treated for malignant diseases continue to improve, yet many survivors face persistent late oral complications that affect function, aesthetics, and quality of life. Oncological therapy, especially at a young age and following head and neck radiotherapy or intensive chemotherapy, can disrupt dental and craniofacial development, resulting in dental developmental disorders, enamel defects, salivary gland dysfunction, caries susceptibility, periodontal problems, trismus, and osteoradionecrosis of the jaw. Although these effects are partially known, they are frequently underrecognized in routine practice, and many children do not receive adequate long-term dental follow-up. A key challenge highlighted in the recent literature is the absence of structured, evidence-based guidelines for monitoring and managing late oral effects. The article emphasizes the need for clearer recommendations, better communication of oncological treatment histories, and stronger integration of dental professionals within survivorship care. Developing standardized follow-up protocols will be essential to ensure timely detection, consistent management, and improved oral health outcomes for childhood cancer survivors. This article is intended as a narrative review, synthesizing available evidence from key publications to highlight clinically relevant late oral complications and gaps in current survivorship care. Full article

Background: While intravenous administration of nanoparticles (NPs) is effective for targeting the lungs and liver, directing them to other organs and tissues remains challenging. Methods: Here, we report alternative administration routes that improve organ-specific accumulation of poly (lactic-co-glycolic acid) (PLGA) NPs (100 nm, negatively charged) loaded with the near-infrared dye Cyanine 7 (Cy7). NP cytotoxicity was evaluated in HEK293, mMSCs, C2C12, L929, and RAW264.7 cells. Hemocompatibility was assessed using WBCs and RBCs. NPs were administered via the tail vein, carotid, renal, and femoral arteries in BALB/c mice. Administration safety was evaluated by laser speckle contrast imaging and histological analysis. NP biodistribution and accumulation were assessed using in vivo and ex vivo fluorescence tomography and confocal microscopy of cryosections. Results: PLGA-Cy7 NPs demonstrate low cytotoxicity even at high doses and exhibit good hemocompatibility. Administration of NPs through the mouse carotid, renal, and femoral arteries significantly increases accumulation in the target ipsilateral brain hemisphere (31.7-fold) and salivary glands (28.3-fold), kidney (13.7-fold), and hind paw (3.6-fold), respectively, compared to intravenous administration. Injection of NPs through arteries supplying the target organs and tissues does not result in significant changes in blood flow, morphological alterations, or irreversible embolization of vessels, provided the procedure is performed correctly and the optimal dosage is used. Conclusions: These results highlight the potential of intra-arterial delivery of NPs for organ-specific drug targeting, underscoring the synergistic impact of advances in materials science, minimally invasive endovascular surgery, and nanomedicine. Full article

Primary Sjögren’s syndrome (pSS) is an autoimmune disease characterized by inflammation and damage to salivary and lacrimal glands. Its etiology involves both genetic and environmental factors. Among susceptibility genes, IRF5 has been highlighted in European populations, but evidence in non-European groups remains limited. This study evaluated whether IRF5 variants rs2004640G/T, rs2070197T/C, rs10954213G/A, and rs59110799G/T are associated with pSS susceptibility, clinical manifestations, or the presence of autoantibodies in a Mexican population. The diagnosis was confirmed by rheumatologists using the 2016 ACR–EULAR classification criteria for pSS. Genotyping was performed using TaqMan probes in 231 controls and 132 pSS patients from central Mexico. Associations were analyzed through binary logistic regression under different genetic models, adjusting for age and geographic origin. Clinical correlations were examined with SNPStats, and haplotypes were constructed using Haploview. Results showed that all four IRF5 variants were significantly associated with pSS susceptibility. Moreover, rs2004640, rs2070197, and rs10954213 variants were associated with arthritis, a frequent clinical manifestation in pSS patients. This represents the first evidence in a Latin American population demonstrating that IRF5 variants contribute to increased risk of developing pSS. These findings suggest ethnicity-specific genetic influences and highlight the importance of expanding research beyond European cohorts. Replication in larger samples and functional analyses are needed to confirm these associations and clarify their biological relevance. Full article

The growth and development of breast cancer are accompanied by an increase in oxidative stress. A close relationship is known to exist between the biological activity of several antioxidant enzymes and the regulation of estrogen-mediated signaling in breast cancer. The aim of this study was to study the activity of salivary antioxidant enzymes and the level of lipid peroxidation products in breast cancer before and after surgical treatment. The study included 115 patients with breast cancer (58.7 ± 10.9 years) and 60 healthy volunteers (51.8 ± 12.1 years). Saliva samples were obtained again from 53 patients 4 weeks after surgery. The content of lipid peroxidation products, catalase activity, total antioxidant activity (AOA) and total peroxidase activity (TPA) in saliva were analyzed before and after breast cancer surgery. An increase in lipid peroxidation products in saliva was observed with positive estrogen receptor expression. For the first time, it was shown that in patients with breast cancer, the levels of salivary TPA and AOA increased, which is likely due to the important role of the salivary glands in antioxidant protection. It can be speculated that the effectiveness of antioxidant defense was associated with estrogen and progesterone receptor expression and was reduced in prognostically unfavorable breast cancer phenotypes (non-luminal and triple-negative breast cancer). Full article

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

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

Sjögren’s disease (SjD), which is also known as Sjögren’s syndrome (SS), is a chronic autoimmune disease characterized by dysfunction of exocrine glands, such as the salivary and lacrimal glands, resulting in xerostomia (dry mouth) and keratoconjunctivitis sicca (dry eyes). Mice in which the SATB1 gene is conditionally deleted in hematopoietic cells (SATB1cKO mice) develop SS as early as 4 weeks of age; however, the etiology of the disease remains to be elucidated. Here, we found that the frequency of abnormally appearing CD4⁺CD8⁺ double positive (DP) T cells in the periphery of SATB1cKO mice was higher in the salivary glands than that in the spleen, suggesting a possible involvement of DP T cells in the pathogenesis of SS in SATB1cKO mice. To investigate the nature of DP T cells, we established DP T cell hybridomas by fusing T cells from the cervical lymph nodes of SATB1cKO mice with the BW5147 thymoma cell line. Among six DP hybridoma clones, the TCRβ gene from five clones exhibited a fetal or immature phenotype. In addition, four out of five clones exhibited upregulated transcription of IL-2 in the salivary glands of T/B cell-deficient RAG2^−/− mice, suggesting that autoreactive T cells were enriched in the DP T cell population of SATB1cKO mice. These results suggest that unusual DP T cells in SATB1cKO mice may be involved in autoimmune pathogenesis in SATB1cKO mice. Full article

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

The sodium iodide symporter (NIS) is a key protein in thyroid function responsible for iodine uptake, and it may be involved in the pathogenesis of autoimmune thyroiditis. However, it is also expressed in the salivary glands, the primary target of autoreactive cells in Sjögren’s syndrome (SS). Given the common link between the two diseases, we computationally investigated whether the epitopes of NIS can trigger an immune response leading to SS in Hashimoto’s thyroiditis (HT) patients genetically predisposed to both diseases. The TepiTool 2016, ABCpred 2006, and DiscoTope 2.0 servers were used to predict T-cell and B-cell epitopes by inputting the FASTA sequences and 3D structures of NIS, thyroid peroxidase (TPO) and Ro60 Y RNA-binding protein (Ro60), which served as reference antigens for HT and SS, respectively. T-cell epitopes were selected based on their binding to a panel of human leukocyte antigen (HLA) alleles associated with both SS and HT. We identified a total of 376 linear T-cell epitopes, 64 linear B-cell epitopes and 68 conformational B-cell epitopes of NIS. Compared to TPO, NIS T-cell epitopes showed significantly lower affinity for HLA alleles (p < 0.0001), while no significant difference was found compared to Ro60. While linear B-cell epitopes of NIS, TPO, and Ro60 showed similar binding affinity, conformational epitopes of NIS were predicted to have higher immunogenicity than Ro60 (p = 0.04), while no significant difference was found compared to TPO. These pivotal findings, discovered by the methods of computer modeling, suggest that NIS can potentially activate T cells and B cells in patients with genetic predisposition to SS and HT and need to be confirmed by further laboratory studies. Full article

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 App^NL–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

Background and Objectives: Sjögren’s syndrome (SS) causes destructive salivary gland dysfunction with substantial oral morbidity. To synthesize practical, evidence-based approaches for early recognition, initial oral management, and timely referral to dental care. Materials and Methods: Narrative review of English-language literature from the Web of Science Core Collection and PubMed, prioritizing systematic reviews, randomized trials, and consensus guidelines. Results: Early oral signs include rapid multifocal root and cervical caries, burning sensations, and rising dental treatment needs. Unstimulated whole saliva ≤ 0.1 mL/min supports significant hypofunction and complements the 2016 ACR/EULAR criteria. Preventive care should combine dietary counseling, salivary stimulation, and topical remineralization. Adjuncts include high-fluoride toothpaste, biomimetic hydroxyapatite dentifrices, and casein phosphopeptide–amorphous calcium phosphate (CPP-ACP). However, evidence for fluoride varnish in SS remains mixed. Pharmacologic sialogogues require screening for contraindications. Conclusions: Embedding oral screening, simple salivary metrics, and a structured referral pathway into rheumatology visits can reduce preventable tooth loss and improve comfort, function, and treatment adherence. Full article