Muscarinic 3 receptor antibodies in Sjögren's disease: Evaluating assay variability and detection methods.

Salivary gland function declines with age, contributing to periodontitis and aspiration pneumonia. However, the cellular mechanisms that preserve secretion during aging remain unclear. Mice were stratified by aging stage, and saliva output and tissue histology were assessed. To infer cell-cell communication, regions surrounding lymphocyte clusters were microdissected and subjected to site-specific single-cell RNA sequencing. Epithelial cell responses were evaluated in a coculture system using a neutralizing antibody. Finally, physiological relevance was assessed by in vivo depletion, followed by quantification of changes in saliva secretion. Saliva production was maintained or modestly increased during early aging stages and coincided with the emergence of lymphoid cell clusters. Single-cell and interactome analyses identified Gzma + ILC1 subsets enriched in aged lymphoid cluster regions and predicted crosstalk with epithelial cells via a GZMA-Pard3 axis. Upregulation of epithelial Aqp5 expression was confirmed in vitro. In vivo depletion of ILC1s in aged mice significantly reduced stimulated saliva output, indicating that local ILC1-derived GZMA supports secretory capacity. Aged submandibular salivary glands accumulated ILC1s that promote epithelial function through a GZMA-dependent pathway and increased AQP5 expression, thereby maintaining salivary secretion during early aging. These findings identify ILC1s as regulators of salivary gland homeostasis and highlight the GZMA-Pard3 axis as a potential therapeutic target.

Background Cigarettes which contain dangerous substances that trigger chronic inflammation is one of highest problem in Indonesia. Long-term smoking can disrupt the immune system and increase the risk of non-communicable diseases for example cancer. Moderate-intensity exercise, like swimming, is believed to positively assist to reducing inflammation and enhancing quality of life. Further researches are necessary to understand the beneficial impact of exercise in preventing chronic inflammation in smokers. Early detection through analysis of IL-8 and TNF-α secretion in saliva is a potential focus in efforts to prevent chronic inflammatory conditions. Objective This research is intended to assess the impact of moderateintensity exercise on the salivary secretion of IL-8 and TNF-α as a preventive measure against chronic inflammation in smokers. Methods Select research subjects who are healthy and given swimming training to measure maximum work capacity. Then the research subjects were divided into 4 groups, carried out a pretest before being given swimming treatment and a posttest after swimming by taking saliva samples using the gargling method for 2 minutes. Next, sample processing and measurement of IL-8 & TNF-α secretion. Then data analysis is carried out. Results There were significant differences between all group in IL-8 secretion (p=0.000 and p=0.005), also different in TNF-α secretion (p=0.160 and p=0.144). Conclusion: Moderate intensity exercise can decrease saliva secretion of IL-8 and TNF-α, so that can used to prevent chronic inflammation in smokers. BJMS, Vol. 25 No. 01 January’26 Page : 176-183

Hard ticks depend upon an ability to precisely and dynamically regulate their saliva to successfully evade host haemostatic and immune defences during extended blood feeding. Although pilocarpine, an exogenous muscarinic acetylcholine receptor (mAChR) agonist, can stimulate salivation experimentally, the endogenous control of saliva secretion by acetylcholine remains poorly understood. Here, we identify and characterise two pharmacologically distinct mAChRs (type A and B) in the genome of the medically important tick Ixodes ricinus. Molecular dynamics simulations and targeted mutagenesis reveal that type B mAChRs exhibit an atypical muscarinic profile, suggesting unconventional receptor signalling. Combining immunolabelling, in vivo pharmacology, and proteomics, we show that specific central neurons interact with distinct salivary gland regions via mAChR type-specific axons, coordinating fluid and protein secretion through separate acini and likely acting upstream of a neuropeptide-dependent cascade. This previously unrecognised mechanism of neural control offers new insights into how ticks modulate their saliva advancing our understanding of vector-host interactions, with potential implications for disrupting pathogen transmission.

As a polyphagous agricultural pest of global significance, Aphis gossypii exhibits substantial population differentiation and inflicts damage across a broad host range, including economically important leguminous crops. This study aimed to clarify the adaptation of three A. gossypii haplotypes (Hap1, Hap3, Hap4) to four legume hosts: cowpea (Vigna unguiculata) varieties Zhongshouluchangfeng (ZLC) and Zhongshoucuichangfeng (ZCC), hyacinth bean (Lablab purpureus) and winged bean (Psophocarpus tetragonolobus). Results showed Hap1 and Hap4 on cowpeas had higher net reproductive rate (R0 > 25) and intrinsic rate of increase (r > 0.36) than on hyacinth bean and winged bean (R0 < 6, r < 0.27). Meanwhile, Hap3 exhibited poor life-table parameters on all legumes. Among legumes, all haplotypes preferred hyacinth bean and refused to feed on winged bean. EPG analysis showed that Hap1 and Hap4 had longer nonprobing time on winged bean, and prolonged xylem ingestion on hyacinth bean. All haplotypes fed longer on cowpea phloem than on hyacinth bean and winged bean. Notably, the proportion of saliva secretion time in the phloem feeding duration of A. gossypii feeding on winged bean exceeded 75%. A. gossypii that fed on cowpeas secreted the highest amount of honeydew CONCLUSION: Different haplotypes of cotton aphids show differentiated adaptability to legumes, and there also is differentiation in the aphid resistance among legumes. These findings can be applied to the formulation of aphid control technologies for legumes and lay a foundation for studying the co-evolution between A. gossypii and their hosts. © 2025 Society of Chemical Industry.

Granulocyte-macrophage colony-stimulating factor (GM-CSF, Csf2) is a potent proinflammatory cytokine1. At steady state, however, GM-CSF has a distinct homeostatic function, being essential for the differentiation and maintenance of alveolar macrophages2-5. Whether macrophage development in nonpulmonary tissues is similarly dependent on GM-CSF is unclear. Here we examine developing tissues of GM-CSF fate-mapping and reporter mice6. We show that type 2 innate lymphoid cells (ILC2s) in the salivary glands produce GM-CSF and identify a macrophage subset that we refer to as 'adenophages'. Adenophages are noncanonical macrophages that are derived from fetal monocytes and are progressively replaced by monocyte-dendritic cell progenitor-derived monocytes. These cells form a spatial niche triad with GM-CSF-producing ILC2s and myoepithelial cells and are required for efficient secretion of saliva. Importantly, adenophages are present throughout exocrine glands, including lacrimal glands and mammary glands, and are also present in humans, indicating a conserved role in exocrine glands across species.

Background and Objectives: Japan’s aging population faces growing challenges related to oral frailty, a condition characterized by the decline of oral function associated with physical and nutritional deterioration. Impaired oral function contributes to reduced chewing, swallowing, and saliva secretion, leading to poor appetite and frailty progression. Ninjin’yoeito (NYT), a traditional Kampo formula, has been clinically used to improve systemic weakness and oral symptoms. This study aimed to evaluate the efficacy and safety of NYT in improving oral health among elderly individuals with impaired oral function. Materials and Methods: In this open-label prospective study, patients received NYT daily for 12 weeks. Assessments included oral symptom scores, mucosal moisture, repetitive saliva swallowing tests (RSST), gustatory function by visual analogue scale (VAS), an 11-item oral questionnaire, and immune profiling by flow cytometry. Safety was assessed through hematological and biochemical tests. Results: Symptom scores decreased from 8.27 at baseline to 3.64 at 12 weeks (p = 0.006), while oral condition scores improved from 5.09 to 1.36 (p = 0.006). Mucosal moisture increased (25.1 to 28.1, p = 0.03), and RSST frequency improved (2.18 to 4.55, p = 0.046). Questionnaire scores declined from 5.1 to 2.0 (p < 0.001). VAS-taste was unchanged overall (p = 0.21) but improved in low baseline patients. Laboratory findings showed no adverse changes, with favorable lipid trends. Immune analysis revealed a decline in NKG2D expression (p = 0.02), whereas other activating and inhibitory markers remained stable. Conclusions: NYT was well tolerated and associated with gradual improvements in oral and physical symptoms among elderly individuals with impaired oral function. These findings provide preliminary evidence supporting the feasibility of Kampo-based approaches for maintaining oral health in aging populations and warrant further validation in larger controlled trials.

Snakehead fish (Channa striata) bones exhibited antibacterial activity against cariogenic bacteria, while Banjar Siam orange (Citrus reticulata) provided complementary antibacterial effects. The combination of these ingredients has the potential to be formulated into a functional saliva-stimulating jelly gum to support oral health in stunted children. This study aimed to obtain an optimal formulation of “Harukam” jelly gum as a saliva stimulant for caries prevention. The research was conducted at the Health Polytechnic of the Ministry of Health Banjarmasin and the Industrial Service Standardization Center Banjarbaru, Indonesia, from June to October 2025. A completely randomized design was applied using four concentrations of snakehead fish bone flour: P0 (0%), P1 (1%), P2 (2%), and P3 (3%). Sensory evaluation was performed using the Hedonic Scale, while the chemical composition was determined through proximate analysis. Optimization was determined using the DeGarmo method, and statistical analysis was performed using the Friedman test. The addition of snakehead fish bone flour significantly affected sensory acceptance (p &lt; 0.001) and increased most proximate values, except for carbohydrates. The P1 formulation received the highest preference score. In conclusion, P1 “Harukam” jelly gum showed potential as a functional food to stimulate saliva secretion and support caries prevention in stunted children.

Saliva specimens are widely used for coronavirus disease 2019 (COVID-19) testing using RT-qPCR due to their advantages over nasopharyngeal swabs of being non-invasive and self-collectable. However, saliva collection can be time-consuming in individuals with reduced saliva secretion, including those with diabetes, diseases involving salivary glands such as Sjögren’s syndrome, and older adults. In this study, we evaluated the diagnostic performance of mouth rinse specimens, which can be easily collected even from individuals with reduced saliva secretion, as an alternative to saliva for RT-qPCR COVID-19 testing. Among the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive specimens analyzed, 88.2% were derived from patients possessing risk factors associated with reduced salivary secretion, including diabetes, use of medications such as anticholinergics or antihistamines, smoking, and older age. The analysis results of mouth rinse specimens demonstrated 96.7% overall agreement with those of saliva specimens, with a sensitivity of 94.1% and specificity of 100%; however, the viral load in the mouth rinse specimens was lower than that in saliva because of sample dilution. These findings suggest that mouth rinse specimens are a practical, versatile, and reliable alternative specimen for RT-qPCR COVID-19 testing.

Engineered nanozyme immunomodulator for xerostomia treatment via regulating submandibular salivary gland

Background. Halitosis is defined as unpleasant mouth odor resulting from pathological, non-pathological, physiological, or systemic conditions. People with halitosis do not always notice the symptoms, which can lead to an underestimation of its prevalence. It greatly embarrasses patients, making them feel insecure in their relationships with others and reducing their quality of life, and its psychological consequences can lead to social anxiety disorders that reduce social interaction. Halitosis can affect productivity, and most patients with halitosis complain of personal discomfort. Objectives: to analyze the literature on current views on halitosis as a psychosocial factor and its relationship to oral health. Materials and Methods. Analytical and bibliosemantic methods were applied in this study. A total of 32 contemporary domestic and international literature sources were reviewed and analyzed during the scientific search. Results and Discussion. Halitosis is classified into true halitosis (intraoral and extraoral), temporary (transient) halitosis, and pseudohalitosis/halitophobia (imaginary bad breath). True halitosis includes two subtypes: physiological and pathological. Pathological halitosis may be intraoral or extraoral. Extraoral halitosis originates in the respiratory system or other body systems. Intraoral halitosis arises from oral cavity diseases such as gingivitis, periodontitis, pericoronitis, necrotizing ulcerative gingivitis/periodontitis, dental caries, oral ulcers, and malignant oral neoplasms, as well as tongue coating, food impaction, xerostomia, and hyposalivation. The unpleasant odor is primarily due to volatile sulfur compounds (VSCs), including hydrogen sulfide and methyl mercaptan, produced by anaerobic bacterial degradation of organic substrates. Their production is influenced by saliva secretion, reduced oxygen concentration, and bacterial metabolism. Temporary bad breath is often caused by food (e.g., garlic, onions, spicy dishes), as well as by alcohol, tobacco, betel, and certain drugs or substances (e.g., solvents, chloral hydrate, nitrites, nitrates, cytotoxic substances, phenothiazines, amphetamines, and formaldehyde). Extraoral halitosis, estimated to account for 5–10% of all cases, can result from diseases of the ear, nose, throat, or respiratory tract, including sinusitis, tonsillitis, bronchiectasis, lung abscess, and malignant tumors of the bronchi and lungs, as well as foreign bodies in the respiratory tract. Systemic conditions such as gastroesophageal reflux disease, diabetes mellitus, carcinoma, liver disease, and kidney disease, along with certain medications (paracetamol, chloral hydrate, dimethyl sulfoxide, disulfiram, nitrates, nitrites, phenothiazines, and amphetamines), may also contribute. In such cases, bacterial activity induces tissue breakdown or necrosis, producing foul-smelling gases released during exhalation. Conclusion. Halitosis, commonly referred to as “bad breath,” is a widespread health problem that significantly impacts quality of life. Identifying the source of halitosis is crucial when a patient seeks medical help. This requires a thorough history of systemic diseases and a comprehensive intraoral examination. The odor may stem from oral conditions or indicate an undiagnosed or emerging systemic disorder, and sometimes reflects a combination of oral and extraoral causes. Dentists should identify and treat oral factors contributing to halitosis, educate patients about proper oral hygiene (including flossing, tongue cleaning, and the correct use of mouthwash and toothpaste), and, when necessary, refer patients to appropriate medical specialists if the problem persists.

Whey protein drinks are an important segment of the functional beverages market, which are commonly consumed as sports drinks due to their high nutritional value and convenience. However, their astringency limits consumer acceptance. This review examines the origin, characterization, and mitigation of astringency in this type of beverage. The main focuses of the article are on the impact of exercise on astringency perception, and the strategies of modulation and optimization of astringency sensation in the design of whey protein drinks. Astringency arises from multiple potential mechanisms, with the interaction between whey proteins, salivary proteins, and oral mucosa leading to reduced lubrication or increased friction as a key contributing mechanism. It is influenced by numerous factors, including pH, protein aggregation state, and dynamic changes within the oral environment. Sensory evaluation and instrumental methods, such as tribological analysis and adsorption techniques, can help quantify the astringency sensation. However, current in vitro analytical models still require optimization to better simulate real oral conditions. Exercise alters saliva secretion (reduced flow rate and changed composition), elevates oral temperature, and modulates taste sensitivity, potentially affecting cross-modal astringency perception. Strategies of mitigation and optimization of astringency sensation include physical, chemical, and biological approaches, all of which improve lubrication or inhibit protein adhesion to reduce astringency. Future research should focus on deepening the current understanding of the behavior of whey protein drinks in the mouth, developing better biomimetic oral models, and designing novel whey protein drinks tailored to the specific needs of athletes, thereby driving market expansion.

BackgroundHuashi Runzao decoction (HRD), a Chinese herbal formula, has been used in clinical practice for patients with primary Sjögren disease (pSD) for years. However, the benefits of HRD for pSD have not been evaluated, and HRD epigenetic mechanism of action remains unexplored.ObjectivesWe conducted a double-blind, randomized, placebo-controlled clinical trial to evaluate the efficacy and safety of HRD in patients with pSD and to explore its epigenetic mechanism of action.MethodsThe clinical scores (including oral dryness, dry eye, dryness, fatigue, and limb pain visual analogue scales scores and the ESSPRI) of pSD patients were recorded at baseline and every 4 weeks thereafter. The disease activity scores (including the ESSDAI and ClinESSDAI), exocrine gland function variables (including the result of Schirmer’s test and salivary flow rate), serological indices (ESR, CRP, IgG, IgA, and IgM) and short-form-36 health survey (SF-36) score were evaluated at baseline and 12 weeks later. Peripheral blood samples were collected from patients and healthy volunteers to determine RNA methylation (m6A and m5C) levels and analyse regulatory factor expression.ResultsHRD improved exocrine gland function in pSD patients and increased saliva (P = 0.049) and tear (P = 0.005) secretion. It also improved patients’ perceptions of subjective symptoms, including oral dryness (P < 0.001), dry eye (P = 0.004), dryness (P = 0.001), and limb pain (P = 0.008) and yielded greater ESSPRIs (P = 0.001), reduced patients’ disease activity according to the ClinESSDAI (P = 0.038) and improved their quality of life. Moreover, HRD increased m6A levels and decreased m5C levels in pSD patients, and HNRNPA2B1 was identified as a potential key epigenetic regulator.ConclusionHRD, a Chinese herbal medicine, may be a promising treatment for pSD, especially for glandular damage. The therapeutic effects of this decoction may be achieved by alteration of the HNRNPA2B1 gene, altering m6A and m5C levels in pSD patients.

Relevance. Evaluation of mineral metabolism markers in mixed saliva may be a non-invasive method for diagnosing potential disorders and developing strategies for the prevention and treatment of dental diseases in children with hypophosphatasia (HPP). Objective: To determine the content of vitamin D, osteocalcin (OCC), osteoprotegerin (OPT), bone-specific alkaline phosphatase (BSAP), and parathyroid hormone (PTH) in mixed saliva and to study their relationships with some clinical parameters of dental status in children with HPP. Materials and Methods. Twenty children with HPP, aged 6–17 years, and 20 healthy children of the same age were examined. Caries intensity and structural and functional caries resistance of enamel in permanent teeth were assessed using the KPU index and the TER test, respectively; periodontal tissue condition was determined using the PMA index. The content of vitamin D, TBPC, OPT, and IAP were determined using enzyme-linked immunosorbent assay (ELISA). Results. Clinical evaluation of key dental parameters in children with HPP and healthy children revealed insufficient oral hygiene associated with an increase in caries in permanent teeth and the presence of moderate gingivitis. In the laboratory phase of the study, a statistically significant difference (2-fold) in the mixed saliva of children with HPP was found in a two-fold decrease in IAP secretion. Reduced levels of vitamin D concentration and OPT minute secretion in mixed saliva in children with HPP are associated with the development of caries in permanent teeth and soft tissue inflammation. Conclusions. The identified changes in biochemical parameters (IBP, vitamin D, OPT, and OPT) in mixed saliva allow us to recommend them as markers for identifying the risk of impaired formation and mineralization of dental and periodontal tissues in children with hypophosphatasia.

Radiation therapy of head and neck cancers frequently leads to irreversible dry mouth that severely compromises the quality of life and is difficult to remedy. Mesenchymal stem cells (MSCs) could ameliorate this adverse effect, but their application is limited by high variations of conventional tissue-derived MSCs and many practical challenges of cell therapies. This study investigated the potential of extracellular vesicles (EVs) from standardized MSCs derived from iPS cells (iMSCs) in ameliorating radiation-caused dry mouth. In a mouse model, locally injected young but not aging iMSC-EVs after radiation preserved saliva secretion and acinar structures. Mechanistically, young iMSC-EVs reversed the acute inhibition of physiological inflammation and chronic increase of pathogenic inflammation in radiated salivary glands, which is related to the preservation of tissue-resident macrophages and polarization of infiltrated macrophages. At both acute and chronic phase after radiation, iMSC-EVs enhanced mitochondria-related cell metabolism pathways such as Oxidative Phosphorylation that modulate cell survival and macrophage polarization. OXPHOS-promoting protein eIF5A and spermidine required for functional eIF5A hypusination are much richer in effective young iMSC-EVs compared with inert aging EVs. Moreover, young iMSC-EV treatment increased hypusinated eIF5A in radiated salivary glands, especially in macrophages. These findings together indicated that iMSC-EVs are a promising cell-free product to restore salivary gland function impaired by radiation, which is mediated by maintaining immune balance and mitochondria-related cell metabolism at both acute and chronic phases.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13287-025-04709-4.

Saliva, a seemingly unpretentious secretion, is actually a multifaceted and multipurpose biofluid. Performing numerous functions, far exceeding only lubrication of oral mucosa, it is essential for general health. Saliva's remarkable properties are primarily due to its constituents, mainly peptides and proteins. Excreted at the entrance to the gastrointestinal tract, this biofluid-active in the oral cavity-also affects other sections of the canal alike, particularly esophagus, where its active components do not undergo degradation. Animal models employing sialoadenectomy consistently with clinical data of patients afflicted with issues related to insufficient salivation, clearly demonstrate how indispensable proper saliva secretion is. In this paper we briefly summarize current perspectives on saliva, with a focus on its protein components and its impact on the upper part of the alimentary tract, particularly on oral and esophageal mucosa. The practical aspects of the modern proteomic research of saliva being at the forefront of salivaomics progress are also discussed, and the current state-of-the-art proteomic methodology is outlined.

Introduction SARS-CoV-2 promotes the occurrence of short and long-term changes in the oral cavity. This study aimed to present the effect of SARS-CoV-2 on the salivary glands. Methods The study group included 138 patients with mild COVID-19 who had various pathologies in the salivary glands. All these patients were treated with antiviral and moisturising agents; some received antibiotics, substances supporting saliva secretion, and saliva substitutes, and some had photobiomodulation and massage of salivary glands. Results In the studied group, statistical significance (α≤0.05) was found for xerostomia, ectasia, and sialadenitis, and other changes were statistically insignificant (α&gt;0.05). Severe dryness was observed in 10% of patients, moderate in 28.33%, and mild in 61.66%. Ectasia was found in 29.71% of cases, sialadenitis in 10%, Sjogren's syndrome in 6.5%, neoplasm in 3.62%, and recurrent sialadenitis was found in 6.5%. Discussion The conducted study indicates that changes located in the salivary glands after SARS-CoV-2 infection are characterized by clinical diversity, occur more often in women, and may be recurrent. Salivary disorders in patients with and after COVID-19 are they impair here quality of oral health and affect the sense of taste, and cause difficulties in eating food. and increase the risk of mental disorders. Conclusion The diseases of the large salivary glands are a significant problem during COVID-19. In the absence of pain and systemic symptoms, observation should be carried out for 4 weeks and wait for spontaneous disappearance. With the simultaneous occurrence of various pathological changes, the patient should be referred for specialist treatment.

Luteolin alleviates hyposalivation by upregulating AQP5 through binding to estrogen receptor β and potentiating the saliva secretion signaling pathway.

Extracellular vesicles derived from salivary gland stem cells cultured on microwell scaffolds loaded with WNT3A promote the recovery of salivary gland function damaged by radiation via the YWHAZ-PI3K-AKT pathway.

Background: This cross-sectional study investigated the associations between medication-induced xerostomia (perceived oral dryness) and intraoral painful aching in 141 middle-aged adults (45–64 years) with self-reported xerostomia resulting from anticholinergic medications. Methods: Xerostomia severity, anxiety, and intraoral painful aching were evaluated using questionnaires, including the semiquantitative Xerostomia Inventory survey. Reduction in saliva secretion (hyposalivation) was objectively assessed by the measurement of unstimulated whole saliva (UWS) flow. Results: Multivariate stepwise linear regression was used to identify factors associated with XI scores, adjusting for potential confounders including age, sex, diabetes, smoking status, and race. The final model identified UWS flow (p = 0.0023), intraoral painful aching (p = 0.0030), and diabetes (p = 0.0097) as significant predictors of xerostomia severity. Anxiety demonstrated a marginal association (p = 0.0643) and accounted for a smaller proportion of model variance. Relative importance analysis revealed that UWS flow contributed 33.16% to the overall model fit, followed by intraoral pain (31.30%), diabetes (23.60%), and anxiety (11.93%). Conclusions: The findings indicate that reduced salivary flow, intraoral discomfort, and the presence of diabetes are significant contributors to xerostomia severity in individuals taking anticholinergic medications. These results highlight the importance of individualized evaluation in xerostomia care and inform targeted clinical strategies for managing xerostomia symptoms in patients with intraoral painful aching, anxiety, or comorbid diabetes.