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Mucins are large, highly glycosylated extracellular matrix proteins that line and protect epithelia of the respiratory, digestive, and urogenital tracts. Previous work has shown that mucins form large, interconnected polymeric networks that mediate their biological functions once secreted. However, how these large matrix molecules are compacted and packaged into much smaller secretory granules within cells prior to secretion is largely unknown. Here, we demonstrate that a small cysteine-rich adaptor protein is essential for proper packaging of a secretory mucin in vivo. This adaptor acts via cysteine bonding between itself and the cysteine-rich domain of the mucin. Loss of this adaptor protein disrupts mucin packaging in secretory granules, alters the mobile fraction within granules, and results in granules that are larger, more circular, and more fragile. Understanding the factors and mechanisms by which mucins and other highly glycosylated matrix proteins are properly packaged and secreted may provide insight into diseases characterized by aberrant mucin secretion.
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Cisteína , Mucinas , Mucinas/metabolismo , Cisteína/metabolismo , Transporte Biológico , Vesículas Secretórias/metabolismoRESUMO
Fluid secretion by exocrine glandular organs is essential to the survival of mammals. Each glandular unit within the body is uniquely organized to carry out its own specific functions, with failure to establish these specialized structures resulting in impaired organ function. Here, we review glandular organs in terms of shared and divergent architecture. We first describe the structural organization of the diverse glandular secretory units (the end-pieces) and their fluid transporting systems (the ducts) within the mammalian system, focusing on how tissue architecture corresponds to functional output. We then highlight how defects in development of end-piece and ductal architecture impacts secretory function. Finally, we discuss how knowledge of exocrine gland structure-function relationships can be applied to the development of new diagnostics, regenerative approaches and tissue regeneration.
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Glândulas Exócrinas/anatomia & histologia , Morfogênese , Animais , Glândulas Exócrinas/embriologia , Glândulas Exócrinas/fisiologia , HumanosRESUMO
An increase in intracellular [Ca2+ ] in exocrine acinar cells resident in the salivary glands or pancreas is a fundamental event that drives fluid secretion and exocytosis of proteins. Stimulation with secretagogues initiates Ca2+ signals with precise spatiotemporal properties thought to be important for driving physiological output. Both in vitro, in acutely isolated acini, and in vivo, in animals expressing genetically encoded indicators, individual cells appear specialized to initiate Ca2+ signals upon stimulation. Furthermore, these signals appear to spread to neighbouring cells. These properties are present in the absence of a conventional pacemaker mechanism dependent on the cyclical activation of Ca2+ -dependent or Ca2+ -conducting plasma membrane ion channels. In this article, we propose a model for 'pacing' intracellular Ca2+ signals in acinar cells based on the enhanced sensitivity of a subpopulation of individual cells and the intercellular diffusion through gap junctions of inositol 1,4,5-trisphosphate and Ca2+ to neighbouring cells.
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Salivary glands have essential roles in maintaining oral health, mastication, taste and speech, by secreting saliva. Salivary glands are composed of several types of cells, and each cell type is predicted to be involved in the carcinogenesis of different types of cancers including adenoid cystic carcinoma (ACC), acinic cell carcinoma (AciCC), salivary duct carcinoma (SDC), myoepithelial carcinoma (MECA) and other histology. In our study, we performed single nucleus RNA-seq on three human salivary gland samples to clarify the gene expression profile of each complex cellular component of the salivary glands and related these expression patterns to expression found in salivary gland cancers (SGC) to infer cell of origin. By single nucleus RNA-seq, salivary gland cells were stratified into four clusters: acinar cells, ductal cells 1, ductal cells 2 and myoepithelial cells/stromal cells. The localization of each cell group was verified by IHC of each cluster marker gene, and one group of ductal cells was found to represent intercalated ductal cells labeled with HES1. Furthermore, in comparison with SGC RNA-seq data, acinar cell markers were upregulated in AciCC, but downregulated in ACC and ductal cell markers were upregulated in SDC but downregulated in MECA, suggesting that markers of origin are highly expressed in some SGC. Cell type expressions in specific SGC histology are similar to those found in normal salivary gland populations, indicating a potential etiologic relationship.
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Carcinoma de Células Acinares , Carcinoma Adenoide Cístico , Carcinoma , Neoplasias das Glândulas Salivares , Humanos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/patologia , Carcinoma Adenoide Cístico/patologia , Carcinoma/patologia , Carcinoma de Células Acinares/metabolismo , RNA/metabolismoRESUMO
Cytomegaloviruses (CMVs) transmit via chronic shedding from the salivary glands. How this relates to the broad cell tropism they exhibit in vitro is unclear. Human CMV (HCMV) infection presents only after salivary gland infection is established. Murine CMV (MCMV) is therefore useful to analyse early infection events. It reaches the salivary glands via infected myeloid cells. Three adjacent spliced genes designated as m131/129 (MCK-2), sgg1 and sgg1.1, positional homologues of the HCMV UL128/130/131 tropism determinants, are implicated. We show that a sgg1 null mutant is defective in infected myeloid cell entry into the salivary glands, a phenotype distinct from MCMV lacking MCK-2. These data point to a complex, multi-step process of salivary gland colonization.
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Muromegalovirus , Glândulas Salivares , Animais , Glândulas Salivares/virologia , Muromegalovirus/genética , Muromegalovirus/fisiologia , Camundongos , Tropismo Viral , Células Mieloides/virologia , Células Mieloides/metabolismo , Proteínas Virais/genética , Proteínas Virais/metabolismo , Infecções por Herpesviridae/virologia , Quimiocinas CCRESUMO
Prosaposin (PSAP), a potent neurotrophic factor, is found in neuronal and non-neuronal tissues and various biological fluids. Neuropathological conditions often alter PSAP production in neural tissues. However, little is known about its alterations in non-neural tissues, particularly in the salivary glands, which are natural reservoirs of various neurotrophic factors. In this study, we explored whether neurotoxic stimulation by kainic acid (KA), a glutamate analog, altered PSAP levels in the salivary system of rats. The results revealed that KA injection did not alter total saliva production. However, KA-induced neurotoxic stimulation significantly increased the PSAP level in the secreted saliva but decreased it in the serum. In addition, KA-induced elevated immunoreactivities of PSAP and its receptors have been observed in the granular convoluted tubule (GCT) cells of the submandibular gland (SMG), a major salivary secretory organ. Indeed, a large number of PSAP-expressing immunogold particles were observed in the secretory granules of the SMG. Furthermore, KA-induced overexpression of PSAP was co-localized with secretogranin in secretory acini (mostly in GCT cells) and the ductal system of the SMG, suggesting the release of excess PSAP from the salivary glands into the oral cavity. In conclusion, the salivary system produces more PSAP during neurotoxic conditions, which may play a protective role in maintaining the secretory function of the salivary glands and may work in distant organs.
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Glândulas Salivares , Saposinas , Ratos , Animais , Glândula Submandibular , Saliva , Proteínas de TransporteRESUMO
PURPOSE: Aplasia of lacrimal and salivary glands (ALSG) is a syndromic disorder characterized by aplasia of lacrimal and salivary systems. Reported ophthalmic manifestations of ALSG include aplasia of lacrimal glands, punctal agenesis, lacrimal sac mucocele, and membranous congenital nasolacrimal duct obstruction (CNLDO). Bony CNLDO, a rare clinical entity, has not been associated with any syndromic disorder. This study investigated the relationship between genetic mutations and bony CNLDO in 3 Chinese families with ALSG. DESIGN: Single-center observational case study. PARTICIPANTS: Three Chinese families with bony CNLDO, including 7 affected and 9 healthy family members. METHODS: Slit-lamp ophthalmic examination, comprehensive physical examination, orbital computed tomography (CT) imaging, cervicofacial magnetic resonance imaging, audiometry, and whole exome sequencing on periphery blood were performed. Variants were cross-referenced with 1000 control genomes and various population databases. Pathologic variants were identified using bioinformatic tools. MAIN OUTCOME MEASURES: Clinical examination, diagnostic imaging, whole exome sequencing, and bioinformatic analysis findings. RESULTS: Affected patients showed decreased tear production on the Schimer I test and reduced tear breakup time. Bony CNLDO was observed on CT, showing unilateral or bilateral bony termination at the middle or terminal segment of the nasolacrimal canal. Magnetic resonance imaging showed aplasia or absence of lacrimal, parotid, and submandibular glands. Physical examination revealed normal ears, digits, and facial morphology. Audiometry and dental assessment were conducted on the pediatric patients and yielded normal results. The clinical characteristics of patients aligned with a diagnosis of ALSG. Genomic analysis revealed 3 novel heterozygous missense mutations of the Fgf10 gene: c.316TâC, c.327CâG, and c.332TâG. The inheritance pattern was autosomal dominant with variable penetrance. These variants were not observed in 1000 control genomes and population databases. These variant positions also were shown to be highly conserved across various animal species. Mutated genes and proteins were predicted as deleterious with most computational models, with a few suggesting they may be benign. CONCLUSIONS: Bony CNLDO was identified as a novel phenotype of ALSG implicated by missense mutations of highly conserved residues in the Fgf10 gene. These cases broadened our knowledge of Fgf10-related phenotypes and prompted clinicians to consider syndromic associations in patients with bony CNLDO. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
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OBJECTIVES: The presence of prostate-specific antigen (PSA) in saliva and salivary glands has been reported. Nevertheless, its release pathway in these glands remains to be elucidated. Here, we showed PSA subcellular distribution focusing on its plausible route in human salivary parenchyma. MATERIALS AND METHODS: Sections of parotid and submandibular glands were subjected to the immunohistochemical demonstration of PSA by the streptavidin-biotin method revealed by alkaline phosphatase. Moreover, ultrathin sections were collected on nickel grids and processed for immunocytochemical analysis, to visualize the intracellular distribution pattern of PSA through the observation by transmission electron microscopy. RESULTS: By immunohistochemistry, in both parotid and submandibular glands PSA expression was detected in serous secretory acini and striated ducts. By immunocytochemistry, immunoreactivity was retrieved in the cytoplasmic compartment of acinar and ductal cells, often associated with small cytoplasmic vesicles. PSA labeling appeared also on rough endoplasmic reticulum and in the acini's lumen. A negligible PSA labeling appeared in most of the secretory granules of both glands. CONCLUSIONS: Our findings clearly support that human parotid and submandibular glands are involved in PSA secretion. Moreover, based on the immunoreactivity pattern, its release in oral cavity would probably occur by minor regulated secretory or constitutive-like secretory pathways.
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Antígeno Prostático Específico , Glândulas Salivares , Humanos , Masculino , Imuno-Histoquímica , Glândula Parótida/ultraestrutura , Antígeno Prostático Específico/metabolismo , Glândulas Salivares/ultraestrutura , Glândula Submandibular/metabolismoRESUMO
AIMS: Low-grade non-intestinal-type sinonasal adenocarcinoma (LGSNAC) is a rare heterogeneous and poorly characterised group of tumours, distinct from intestinal- and salivary-type neoplasms. Therefore, further characterisation is needed for clearer biological understanding and classification. METHODS AND RESULTS: Clinical, histological and molecular characterisation of four cases of biphasic, low-grade adenocarcinomas of the sinonasal tract was performed. All patients were male, aged between 48 and 78 years, who presented with polypoid masses in the nasal cavity. Microscopically, virtually all tumours were dominated by tubulo-glandular biphasic patterns, microcystic, focal (micro)papillary, oncocytic or basaloid features. Immunohistochemical staining confirmed biphasic differentiation with an outer layer of myoepithelial cells. Molecular profiling revealed HRAS (p.G13R, p.Q61R) mutations, and concomitant AKT1 (p.E17K, p.Q79R) mutations in two cases. Two cases showed potential in-situ/precursor lesions adjacent to the tumour. Follow-up periods ranged from 1 to 30 months, with one case relapsing locally after 12 and > 20 years. CONCLUSION: This study further corroborates a distinct biphasic low-grade neoplasm of the sinonasal tract with seromucinous differentiation. Although morphological and molecular features overlap with salivary gland epithelial-myoepithelial carcinoma, several arguments favour categorising these tumours within the spectrum of LGSNAC.
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OBJECTIVE: To assess the construct validity of the novel Outcome Measures in Rheumatology (OMERACT) ultrasound (US) semiquantitative scoring system for morphological lesions in major salivary glands by comparing it with magnetic resonance imaging (MRI) and unstimulated whole salivary flow rates (U-WSFRs) in patients with primary Sjögren syndrome (pSS). METHODS: Nine sonographers applied the OMERACT 0-3 grayscale scoring system for parotid (PGs) and submandibular glands (SMGs) in 11 patients with pSS who also had MRIs performed. These were evaluated by 2 radiologists using a semiquantitative 0-3 scoring system for morphological lesions. The agreement between US and MRI and the association between U-WSFRs and imaging structural lesions was determined. A score ≥ 2 for both US and MRI was defined as gland pathology. RESULTS: The prevalence of US morphological lesions in 11 patients with a score ≥ 2 was 58% for PGs and 76% for SMGs, and 46% and 41% for PGs and SMGs, respectively, for MRI. The agreement between OMERACT US scores and MRI scores was 73-91% (median 82%) in the right PG and 73-91% (median 91%) in the left PG, 55-91% (median 55%) in the right SMG and 55-82% (median 55%) in the left SMG. When relations between the presence of hyposalivation and an US score ≥ 2 were examined, agreement was 91-100% (median 83%) in both PGs and 55-91% (median 67%) in both SMGs. CONCLUSION: There is moderate to strong agreement between the OMERACT US and MRI scores for major salivary glands in patients with pSS. Similar agreement ratios were observed between the higher OMERACT US scores and presence of hyposalivation.
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Síndrome de Sjogren , Xerostomia , Humanos , Síndrome de Sjogren/diagnóstico por imagem , Glândulas Salivares/diagnóstico por imagem , Ultrassonografia , Xerostomia/diagnóstico por imagem , Imageamento por Ressonância MagnéticaRESUMO
The current study aimed to investigate the effects of ageing on oral immunity using ß-defensin (DEFB) 1/2 as a marker and evaluate the effects of curcumin (CUR) on these processes. The study sample included thirty male C57BL/6J mice divided into three groups based on the treatment method used. The young control (YC) and old control (OC) groups received 0·5 % methylcellulose-400 (CUR vehicle) orally for 5 days, whereas the CUR group of older mice received a CUR solution suspended in 0·5 % methylcellulose-400 (dose: 3·0 mg/kg body). DEFB1/2 and immune indicator levels were measured in the saliva and salivary glands post-treatment. The saliva volume and protein content were significantly reduced in the OC group compared with the YC group. CUR administration restored these parameters, decreased DEFB1 expression in the salivary gland and increased DEFB1/2 secretion and DEFB2 expression. These findings were supported by epigenetic gene regulation and partial cytokine activation from changes in WD40 repeat protein 5, TNF alpha and IL-1beta. CUR can partially restore age-related changes in oral immune responses and promote oral health, thereby preventing frailty in the older population through a nutritional therapeutic pathway.
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Envelhecimento , Curcumina , Camundongos Endogâmicos C57BL , Saliva , beta-Defensinas , Animais , Curcumina/farmacologia , Curcumina/administração & dosagem , Masculino , Saliva/metabolismo , Saliva/química , Camundongos , beta-Defensinas/metabolismo , beta-Defensinas/genética , Glândulas Salivares/efeitos dos fármacos , Glândulas Salivares/metabolismo , Glândulas Salivares/imunologia , Interleucina-1beta/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
PURPOSE: A MASCC/ISOO Clinical Practice Statement (CPS) is aimed at generating a concise tool for clinicians, which concentrates practical information needed for the management of oral complications of cancer patients. This CPS is focused on the management of oral manifestations of chronic graft-versus-host-disease (cGVHD). METHODS: This CPS was developed based on critical evaluation of the literature followed by a structured discussion of a group of leading experts, members of the Oral Care Study Group of MASCC/ISOO. The information is presented in the form of succinct bullets and table to generate a short manual about the best standard of care. RESULTS: The treatment goals in oral cGVHD are to relieve pain and xerostomia, improve oral function, prevent secondary infection, prevent deterioration of the dentition, and detect malignant transformation as early as possible. The prevention and treatment measures for oral mucosal lesions, hypofunction of the salivary glands, and sclerodermatous changes in the oral and perioral tissues are detailed, as well as the possible complications and side effects of these interventions. CONCLUSIONS: Patients post allogeneic hematopoietic cell transplantations, with cGVHD manifest in the oral and perioral tissues, should be regularly monitored and treated as needed by an oral care practitioner. This CPS provides the clinician with practical tools for examining, preventing, and treating the various sequalae that may affect the oral cavity in these patients.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Doenças da Boca , Doença Enxerto-Hospedeiro/terapia , Doença Enxerto-Hospedeiro/etiologia , Humanos , Doenças da Boca/etiologia , Doenças da Boca/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Doença Crônica , Xerostomia/etiologia , Xerostomia/terapiaRESUMO
The aim of the study is to expound the effect of psoriasis on salivary glands by evaluating the secretion of saliva and salivary cytokine biomarkers in patients with psoriasis. This study was conducted by recruiting 120 subjects that included 60 patients diagnosed clinically with active psoriasis and 60 healthy controls who were age and gender matched to psoriatic subjects. Unstimulated whole saliva was collected from all the subjects by spitting method, and levels of tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin-2 (IL-2), and IL-10 (IL-10) were determined via enzyme-linked immunosorbent assay (BT Lab, Shanghai, China). Secretion of saliva in psoriasis patients was considerably reduced than in healthy controls. The concentrations of pro-inflammatory cytokines (TNF-α, IFN-γ, and IL-2) were significantly increased, whereas level of anti-inflammatory cytokine (IL-10) was markedly decreased in the saliva of psoriasis patients with hyposalivation compared to healthy subjects. Our results demonstrated significant negative correlation of salivary flow rates with the disease severity. No significant correlations were obtained between salivary levels of tested cytokines and salivary flow rates in our study. Findings of the study reflect inflammation of salivary glands with reduced salivary flow rates in psoriasis patients. The inflammatory responses in salivary gland tissues by virtue of increased pro-inflammatory cytokines concentrations together with lower anti-inflammatory cytokine levels may have a role in affecting the saliva secretion in psoriasis patients. Secretion of unstimulated saliva in psoriasis patients decreases with the severity and duration of the disease.
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Biomarcadores , Citocinas , Psoríase , Humanos , Psoríase/metabolismo , Masculino , Feminino , Citocinas/metabolismo , Citocinas/análise , Biomarcadores/análise , Biomarcadores/metabolismo , Adulto , Pessoa de Meia-Idade , Saliva/metabolismo , Saliva/química , Xerostomia/metabolismo , Índice de Gravidade de Doença , Inflamação/metabolismoRESUMO
Stomoxys calcitrans L. (Diptera: Muscidae), the stable fly, is a hematophagous insect of great veterinary importance, because it is a mechanical vector of diverse pathogens in livestock. The saliva of blood-feeding insects presents important pharmacologically active molecules that impair blood clotting, promote vasodilation and modulate the host immune system response, crucial processes for successful feeding. These properties also enable pathogens' transmission. In the present work, we describe an efficient protocol to dissect S. calcitrans salivary glands, their morphological characteristics and lipid profile. The mean length of the tubular gland is 3.23 mm with a bulbous posterior end and a narrow anterior end. Histological analysis revealed a monolayer of large polygonal epithelial cells with voluminous nuclei and high lipid content in their cytoplasm. Ultrastructural analysis showed that the epithelium is rich in mitochondria, free ribosomes, Golgi complex cisternae, presenting a great extension of rough endoplasmic reticulum that contains an electron-dense material. Lipid analysis by thin-layer chromatography showed that neutral fatty acids and phosphatidylcholine are predominant in the fly salivary glands. Lysophosphatidylcholine, an important signalling biomolecule involved in different metabolic processes, including host's immunomodulation and pathogens proliferation and differentiation, is also present.
Stomoxys calcitrans L. (Diptera: Muscidae), a moscadosestábulos, é um inseto hematófago de grande importância veterinária, uma vez que é vetor mecânico de diversos patógenos que infectam animais da pecuária. A saliva de insetos que se alimentam de sangue apresenta importantes moléculas farmacologicamente ativas que impedem coagulação sanguínea, promovem vasodilatação e modulam o sistema imune do hospedeiro, processos cruciais para uma alimentação bem sucedida. Tais propriedades também permitem a transmissão de patógenos. No presente trabalho, nós descrevemos um protocolo eficiente para dissecar as glândulas salivares de S. calcitrans, suas características morfológicas e perfil lipídico. O comprimento médio da glândula tubular é 3.23 mm com uma porção posterior bulbosa e porção anterior estreita. Análises histológicas revelaram uma monocamada de células epiteliais largas e poligonais com núcleos volumosos e alto conteúdo lipídico em seus citoplasmas. Análises ultraestruturais mostraram um epitélio rico em mitocôndria, ribossomos livres, cisternas do complexo de Golgi, apresentando uma grande extensão de retículo endoplasmático que contém um material eletrodenso. A análise lipídica mostrou que ácidos graxos neutros e fosfatidilcolina predominam nas glândulas salivares da mosca. Lisofosfatidilcolina, uma importante biomolécula sinalizadora envolvida em diferentes processos metabólicos, incluindo imunomodulação do hospedeiro e proliferação e diferenciação de patógenos, também se encontra presente.
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Alpha-Gal/α-Gal is an oligosaccharide produced by non-primate mammals. Humans have developed an immune response mediated by anti-α-Gal antibodies that can trigger an allergic reaction and cause anaphylaxis. In recent years, cases of patients with delayed allergic reaction to mammalian meat have been reported worldwide. In Spain, these cases have been related to the species Ixodes ricinus L. (Ixodida: Ixodidae), whose distribution is located in the north of the country. In this work, the presence of α-Gal in water-soluble extracts from samples of salivary glands and digestive tracts of Hyalomma lusitanicum Koch (Ixodida: Ixodidae) both engorged and collected from vegetation were studied. The presence of that epitope was confirmed by the presence of reactive proteins of >250 kDa in both samples. The highest concentrations of α-Gal were detected in salivary glands. Neither sex nor diet influenced the concentration of α-Gal, which seems to indicate its endogenous production and its possible inoculation to the host during tick feeding.
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Hipersensibilidade Alimentar , Ixodidae , Animais , Ixodidae/imunologia , Feminino , Hipersensibilidade Alimentar/imunologia , Masculino , Glândulas Salivares , Espanha , Epitopos , Carne Vermelha/análise , Dissacarídeos/análiseRESUMO
OBJECTIVE: Salivary glands are frequently damaged in patients undergoing radiotherapy for head and neck cancer. Whether PANoptosis, which is characterized by pyroptosis, apoptosis, and necroptosis, occurs during radiation injury to the salivary glands and its role remain unclear. MATERIALS AND METHODS: Radiation-induced injury models of mouse submandibular gland, as well as primary acinar cells and HSG cell lines were established to determine the presence of radiation-induced PANoptosis. Several programmed cell death inhibitors, PFTα, disulfiram, Nec-1 and zVAD, were used to compare the effects of different cell death pathway on radiation injury. The LEGENDplex™ Human Inflammation Panel was used to characterize the inflammatory landscape secreted by salivary gland cells after radiotherapy. RESULTS: Single 15Gy or 8Gy radiotherapy triggered PANoptosis in mouse submandibular gland or salivary gland cells. Compared to the suppression of pyroptosis, apoptosis, or necroptosis alone, the inhibition of PANoptosis is more effective in preventing radiation injury to the salivary glands (p < 0.0001). The levels of multiple inflammatory cytokines were significantly up-regulated in the supernatants of HSG cells within 48 h after IR. Neutralizing inflammatory cytokines are capable of inhibiting salivary glands PANoptosis. CONCLUSIONS: Inhibition of PANoptosis induced by inflammatory cytokines can effectively prevent radiation injury of salivary glands.
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OBJECTIVE: Carcinoma ex-pleomorphic adenoma (CEXPA) represents a malignant transformation from a recurrent or primary pleomorphic adenoma (PA), and the immune response may be essential in this process. Therefore, in this study, we aimed to identify and quantify subpopulations of dendritic cells (DCs) in CEXPA, residual PA in CEXPA (rPA), and PA. MATERIALS AND METHODS: A multicenter study was performed collecting salivary gland tumor (SGT) samples from three Oral and Maxillofacial Pathology Centers. A tissue microarray containing 41 samples of CEXPA and 22 samples of PA was included in this study and submitted to immunohistochemical reactions against CD1a, CD83, CD207, and Ki67 antibodies. RESULTS: Both PA and rPA showed a higher quantification of CD207+ and CD83+ cells when compared to CEXPA (p < 0.001 and p < 0.01, respectively). There was also a difference when comparing the cell proliferation index between PA/rPA and CEXPA using the Ki-67 marker (p = 0.043). However, there was no difference in the DC population regarding clinical parameters such as sex, anatomical location, size, and metastases (p > 0.06). CONCLUSIONS: Immunohistochemical profile of DC subpopulations and cell proliferation biomarkers in SGTs can contribute as an important tool in the differentiation of benign and malignant tumors or detection of initial areas with malignant transformation.
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The Asian citrus psyllid, Diaphorina citri Kuwayama (Hemiptera: Psyllidae), is the key vector insect transmitting the Candidatus Liberibacter asiaticus (CLas) bacterium that causes the devastating citrus greening disease (Huanglongbing, HLB) worldwide. The D. citri salivary glands (SG) exhibit an important barrier against the transmission of HLB pathogen. However, knowledge on the molecular mechanism of SG defence against CLas infection is still limited. In the present study, we compared the SG transcriptomic response of CLas-free and CLas-infected D. citri using an illumine paired-end RNA sequencing. In total of 861 differentially expressed genes (DEGs) in the SG upon CLas infection, including 202 upregulated DEGs and 659 downregulated DEGs were identified. Functional annotation analysis showed that most of the DEGs were associated with cellular processes, metabolic processes, and the immune response. Gene ontology and Kyoto Encyclopaedia of Genes and Genomes enrichment analyses revealed that these DEGs were enriched in pathways involving carbohydrate metabolism, amino acid metabolism, the immune system, the digestive system, the lysosome, and endocytosis. A total of 16 DEGs were randomly selected to further validate the accuracy of RNA-Seq dataset by reverse-transcription quantitative polymerase chain reaction. This study provides substantial transcriptomic information regarding the SG of D. citri in response to CLas infection, which may shed light on the molecular interaction between D. citri and CLas, and provides new ideas for the prevention and control of citrus psyllid.
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Hemípteros , Glândulas Salivares , Transcriptoma , Animais , Hemípteros/microbiologia , Hemípteros/genética , Glândulas Salivares/microbiologia , Glândulas Salivares/metabolismo , Doenças das Plantas/microbiologia , Citrus/microbiologia , LiberibacterRESUMO
Recently, significant advances in the molecular characterization of salivary gland neoplasms have facilitated the classification and diagnosis of specific diagnostic entities. In the highly challenging diagnostic scenario of salivary malignancies, molecular testing is increasingly being adopted in routine practice to refine the cytological diagnosis of salivary lesions. Here, we reviewed the most recent evidence in the field of salivary glands molecular cytopathology.
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Neoplasias das Glândulas Salivares , Glândulas Salivares , Humanos , Biópsia por Agulha Fina , Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/diagnóstico , Neoplasias das Glândulas Salivares/genética , Técnicas de Diagnóstico Molecular , Estudos RetrospectivosRESUMO
BACKGROUND: Metastatic lesions to the salivary gland are rare and mostly affect the parotids. Metastases represent 8% of all malignant lesions of the parotid gland. Around 80% originate from squamous cell carcinomas (SCC) of the head and neck region. Fine needle aspiration (FNA) plays a crucial role in distinguishing primary salivary gland lesions from metastases. Herein we describe our series of metastases to the parotid glands. MATERIALS AND METHODS: We analysed 630 parotid gland FNAs over a decade including conventional and liquid-based cytology specimens. Ancillary techniques such as immunocytochemistry (ICC) were conducted on cell blocks. RESULTS: Eighty (12.4%) cases were malignant lesions, of which 53 (63.75%) were metastases including 24% melanoma, 22.6% SCC, 19% renal carcinomas, 7.5% breast carcinomas, 11.3% lung, 9% intestinal and 1.8% testicular, malignant solitary fibrous tumour and Merkel cell carcinoma. The 53 cases, classified according to the Milan system for salivary cytopathology, belonged to 5 Suspicious for malignancy (SFM) and 48 malignant (M) categories. Forty had a known history of primary malignancy (75.4%), while 13 were suspicious to be a metastatic localisation (24.5%), distributed as 5SFM (2SCC and 3Melanoma) and 8 M. A combination of clinical history, cytomorphology and ICC identified 100% of them. CONCLUSIONS: Fine needle aspiration plays a central role in the diagnostic workup of patients with metastatic lesions to their parotid glands, thereby defining the correct management. Diagnostic accuracy may be enhanced by applying ICC. Although melanoma and SCC are the most common histological types, several other malignancies may also metastasize to the parotid glands and should be kept into consideration.