Saliva Research Articles

The Remineralization of Enamel from Saliva: A Chemical Perspective

The natural remineralization of enamel is of major importance for oral health. In principle, early erosions (demineralization) induced by acidic beverages and foods as well as initial caries lesions can be covered and remineralized by the deposition of calcium phosphate, i.e., tooth mineral. This remineralization effect is characterized by the presence of calcium and phosphate ions in saliva that form hydroxyapatite on the enamel surface. Although it is apparently a simple crystallization, it turns out that remineralization under in vivo conditions is actually a very complex process. Calcium phosphate can form a number of solid phases of which hydroxyapatite is only one. Precipitation involves the formation of metastable phases like amorphous calcium phosphate that convert into biological apatite in a number of steps. Nanoscopic clusters of calcium phosphate that can attach on the enamel surface are also present in saliva. Thus, remineralization under strictly controlled in vitro conditions (e.g., pH, ion concentrations, no additives) is already complex, but it becomes even more complicated under the actual conditions in the oral cavity. Here, biomolecules are present in saliva, which interact with the forming calcium phosphate mineral. For instance, there are salivary proteins which have the function of inhibiting crystallization to avoid overshooting remineralization. Finally, the presence of bacteria and an extracellular matrix in plaque and the presence of proteins in the pellicle have strong influences on the precipitation on the enamel surface. The current knowledge on the remineralization of the enamel is reviewed from a chemical perspective with a special focus on the underlying crystallization phenomena and the effects of biological compounds that are present in saliva, pellicle, and plaque. Basically, the remineralization of enamel follows the same principles as calculus formation. Notably, both processes are far too complex to be understood on a microscopic basis under in vivo conditions, given the complicated process of mineral formation in the presence of a plethora of foreign ions and biomolecules.

Prediction of Oral Cancer Biomarkers by Salivary Proteomics Data.

Oral cancer, representing 2-4% of all cancer cases, predominantly consists of Oral Squamous Cell Carcinoma (OSCC), which makes up 90% of oral malignancies. Early detection of OSCC is crucial, and identifying specific proteins in saliva as biomarkers could greatly improve early diagnosis. Here, we proposed a strategy to pinpoint candidate biomarkers. Starting from a list of salivary proteins detected in 10 OSCC patients and 20 healthy controls, we combined a univariate approach and a multivariate approach to select candidates. To reduce the number of proteins selected, a Protein-Protein Interaction network was built to consider only connected proteins. Then, an over-representation analysis (ORA) determined the enriched pathways. The network from 172 differentially abundant proteins highlighted 50 physically connected proteins, selecting relevant candidates for targeted experimental validations. Notably, proteins like Heat shock 70 kDa protein 1A/1B, Pyruvate kinase PKM, and Phosphoglycerate kinase 1 were suggested to be differentially regulated in OSCC patients, with implications for oral carcinogenesis and tumor growth. Additionally, the ORA revealed enrichment in immune system, complement, and coagulation pathways, all known to play roles in tumorigenesis and cancer progression. The employed method has successfully identified potential biomarkers for early diagnosis of OSCC using an accessible body fluid.

Ultrasound and its coupled oak blocks treatment based on absorbed energy density for comprehensive insight and scale-up consideration of phenolic and astringency profiles in red wines

Ultrasound and ultrasound-coupled oak blocks techniques on the phenolic and astringency profiles of Petit Verdot wines were discussed in this study. The relationship between techniques at varying absorbed energy density (AED) gradients and astringency was revealed, elucidating potential molecular mechanisms regarding compound interactions. Ultrasound was found to promote phenolics degradation and condensed tannins maturation, while oak blocks improved ellagitannins release into wines, facilitating polycondensation reactions to form larger complexes. Phenolics binding to salivary proteins decreased at low AED values (0–33.07 J/mL), enhanced at high AED values (66.14–165.34 J/mL), and reduced salivary proteins' precipitation ability. Treated samples significantly altered astringency's global terminology and sensory attributes across oral regions, with oak blocks enriching the astringency hierarchy. Multivariate analysis identified an optimal ultrasound AED of 0 to 33.07 J/mL, and an effective PLS-DA model was developed for industrial scale-up considerations, aiming to cost-effectively enhance the organoleptic quality of wines.

Co-spray drying whey protein isolate with polysaccharides provides additional lubrication impacting the sensory profile of model beverages

For older adults, whey protein is associated with negative sensory attributes, including undesirable mouthfeel qualities, that limit consumption and acceptance. Previous work suggests that increased lubrication may have the ability to reduce whey protein-associated mouthdrying, a driver for disliking, by limiting interactions of whey protein with salivary proteins and mucin. This was investigated in the current study by co-spray drying whey protein with combinations of maltodextrin, xanthan gum and/or guar gum; the resulting powders were used to make 10% suspensions. The particle size, zeta potential, rheological and tribological profiles of these suspensions were measured. It was shown that co-spray drying whey protein with guar gum led to a reduction in instrumental friction, irrespective of changes in viscosity. These samples were perceived as significantly more mouthcoating and smooth when assessed by a trained sensory panel. Contrastingly, suspensions containing xanthan gum showed increased viscosity and enhanced shear thinning compared with whey protein, but no change in instrumental friction at higher sliding speeds. This may be a result of a larger particle size, representing increased aggregation in samples containing xanthan gum. There was no significant difference in mouthdrying or slipperiness perception between the suspensions. These findings suggest that the incorporation of guar gum has the capacity to reduce oral friction and impact mouthfeel in whey protein model beverages. This should be taken forward into temporal sensory trials to further investigate the effects of additional lubrication.

Explorative study of stimulated saliva proteome in head and neck cancer patients pre- and post-treatment

Objectivesto compare saliva proteome of patients before treatment of head and neck cancer and six months post-treatment with controls. DesignFive dentate patients and five age and gender-matched controls were included. The stimulated salivary secretion rate was determined, and saliva was stored at −80 °C. After thawing, 30 mg of each sample and a reference (aliqouts of all samples) was trypsin digested. The digested peptides were analyzed by mass spectrometry. The relative abundances were transformed to log2 and significant differences determined. Relative abundances of mucins were compared with patient's problems with dry mouth, sticky saliva and swallowing. Data are available via ProteomeXchange with identifier PXD047500. Results966 proteins with ≥2 unique peptides were found. Compared with controls, 30 proteins were found in significantly lower relative abundances and 65 in higher at pre-treatment and 38 proteins in significantly lower relative abundances and 34 proteins in higher post-treatment. Regarding proteins from the salivary glands, a significantly lower relative abundance of Cystatins was detected pre-treatment and significantly lower relative abundances of Cystatin, Cysteine-rich secretory protein 3, Lactoperoxidase, Prolactin-inducible protein and Proline-rich protein 4 post-treatment. No clear relation between relative abundance of mucins and dry mouth, sticky saliva and problems with swallowing was detected. ConclusionDecreases in several salivary gland proteins post cancer treatment might lead to a reduced defense against oral disorders. Knowledge about changes in saliva proteins in connection with oral cancer treatment is important for planning dental care for these patients.

Salivary cysteine levels as a potential biochemical indicator of oral cancer risk in tobacco consumers.

Aim: Oral cancer is the leading cause of mortality, with a survival rate of less than 5 years, and is predominantly influenced by tobacco mutagens. Invasive diagnostic methods hinder early detection of oral cancer biomarkers. The present study performed salivary biochemical analysis for early oral cancer screening in tobacco consumers.Materials & methods: Three study groups included healthy controls (n=25), tobacco users (n=25) and oral cancer patients (n=25). Salivary total protein, amylase, TNF-α and amino acid levels were evaluated using enzymatic tests, Enzyme linked Immunosorbent Assay (ELISA) and High-Performance Liquid Chromatography (HPLC).Results: Compared with healthy controls, salivary total protein and TNF-αlevels were significantly (p=0.04) higher in oral cancer patients. Salivary amylase levels were significantly lower in tobacco smokers (p=0.02) and higher in oral cancer patients (p=0.01). Interestingly, the amino acid cysteine concentration was significantly higher (p=0.02) in tobacco consumers (62.5±10) than in healthy controls (116.1±28).Conclusion: In high-risk populations, such as tobacco users, salivary biochemical analysis can serve as a promising noninvasive diagnostic method for early oral cancer screening. As a salivary biomarker, the amino acid cysteine exhibits potential as a means of detecting the progression of oral cancer in individuals who consume tobacco.

Exploring the Relationship Between Stress, Salivary C-Reactive Protein, and Embodied Physiological Responses in a Nigerian Population.

The impacts of stress on inflammation, although hypothesized, have not been thoroughly examined, especially in relation to social and environmental factors and particularly within Black populations. This study aims to explore the biological mechanisms of embodiment linking stress and health to understand physiological changes in the body's response to psychological stress in a Nigerian population. Through a multidisciplinary approach, this study queries the relationship between stress, cortisol, and salivary C-reactive protein (sCRP), a biomarker of inflammation, while also validating the use of sCRP as a potential and accurate stress indicator in the field. In this cross-sectional study, 138 passive drool saliva samples (nfemale = 89 nmale = 49) were collected and assessed for sCRP and cortisol levels in adults. Participants also completed a short demographic survey and, to measure psychological stress, the General Health Questionnaire 12 (GHQ-12). Relationships between sCRP and stress-related variables (i.e., cortisol, GHQ-12, and demographic data) were assessed using Spearman's correlations, simple regression, multivariable linear regression, and exploratory factor analysis. sCRP levels ranged from 20.57 to 6879.41 pg/mL across all samples, with significant differences between female and male participants. The GHQ-12 was not a significant predictor of sCRP variability. However, socio-demographic factors such as body mass index (BMI), age, self-reported sex, ethnic identity, and cortisol were significant predictors, collectively explaining 24%-27% of the variation in sCRP. Socio-demographic predictors like BMI, age, sex, and particularly ethnic group experience in Nigeria encapsulate aspects of embodied stress, that significantly affect sCRP variability.

Oral SARS-CoV-2 host responses predict the early COVID-19 disease course

Oral fluids provide ready detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and host responses. This study sought to evaluate relationships between oral virus, oral and systemic anti-SARS-CoV-2-specific antibodies, and symptoms. Oral fluids (saliva/throat wash (saliva/TW)) and serum were collected from asymptomatic and symptomatic, nasopharyngeal (NP) SARS-CoV-2 RT-qPCR+ human participants (n = 45). SARS-CoV-2 RT-qPCR and N-antigen detection by immunoblot and lateral flow assay (LFA) were performed. RT-qPCR for subgenomic RNA (sgRNA) was sequence confirmed. SARS-CoV-2-anti-S protein RBD LFA and ELISA assessed IgM and IgG responses. Structural analysis identified host salivary molecules analogous to SARS-CoV-2-N-antigen. At time of enrollment (baseline, BL), LFA-detected N-antigen in 86% of TW and was immunoblot-confirmed. However, only 3/17 were saliva/TW qPCR+ . Sixty percent of saliva and 83% of TW demonstrated persistent N-antigen at 4 weeks. N-antigen LFA signal in three anti-spike sero-negative participants suggested potential cross-detection of 4 structurally analogous salivary RNA binding proteins (alignment 19–29aa, RMSD 1–1.5 Angstroms). At enrollment, symptomatic participants demonstrated replication-associated sgRNA junctions, were IgG+ (94%/100% in saliva/TW), and IgM+ (63%/54%). At 4 weeks, SARS-CoV-2 IgG (100%/83%) and IgM (80%/67%) persisted. Oral and serum IgG correlated 100% with NP+ PCR status. Cough and fatigue severity (p = 0.010 and 0.018 respectively), and presence of weakness, nausea, and composite upper respiratory symptoms (p = 0.037, 0.005, and 0.017, respectively) were negatively associated with saliva IgM but not TW or serum IgM. Throat wash IgM levels were higher in women compared to men, although the association did not reach statistical significance (median: 290 (female) versus 0.697, p = 0.056). Important to transmission and disease course, oral viral replication and persistence showed clear relationships with select symptoms and early oral IgM responses during early infection. N-antigen cross-reactivity may reflect mimicry of structurally analogous host proteins.

Mosquito salivary apyrase regulates blood meal hemostasis and facilitates malaria parasite transmission

The evolution of hematophagy involves a series of adaptations that allow blood-feeding insects to access and consume blood efficiently while managing and circumventing the host’s hemostatic and immune responses. Mosquito, and other insects, utilize salivary proteins to regulate these responses at the bite site during and after blood feeding. We investigated the function of Anopheles gambiae salivary apyrase (AgApyrase) in regulating hemostasis in the mosquito blood meal and in Plasmodium transmission. Our results demonstrate that salivary apyrase, a known inhibitor of platelet aggregation, interacts with and activates tissue plasminogen activator, facilitating the conversion of plasminogen to plasmin, a human protease that degrades fibrin and facilitates Plasmodium transmission. We show that mosquitoes ingest a substantial amount of apyrase during blood feeding, which reduces coagulation in the blood meal by enhancing fibrin degradation and inhibiting platelet aggregation. AgApyrase significantly enhanced Plasmodium infection in the mosquito midgut, whereas AgApyrase immunization inhibited Plasmodium mosquito infection and sporozoite transmission. This study highlights a pivotal role for mosquito salivary apyrase for regulation of hemostasis in the mosquito blood meal and for Plasmodium transmission to mosquitoes and to the mammalian host, underscoring the potential for strategies to prevent malaria transmission.

First Insight into Lignin Valorization as a Promising Biopolymer for the Modulation of the Physicochemical Properties of Port Wine.

Lignosulfonate (LS), kraft lignin (KL), and organosolv lignin (OL) were evaluated as potential modulating agents of the physicochemical properties of Port wine at two different concentrations for 7 and 30 days. KL and LS demonstrated the ability to remove proteins and potentiate the anthocyanin concentration. LS reduced the tannin content and the interaction of salivary acidic proline-rich proteins with wine phenolic compounds. None of the lignin promoted a perceptible color change; however, the yellowish color of KL and OL at 100 g/hL contributed to an increase in the yellow tones of wines. Lignin improved wine aroma by reducing the amount of unwanted volatiles by 30% and increasing the content of ethyl esters associated with fruity aromas by up to 60%. The results suggest that lignin, especially LS, can be employed as a modulating agent, positively impacting wine's physicochemical properties. This valorization of a byproduct opens up new opportunities for the wine industry.

Searching for Protein Off-Targets of Prostate-Specific Membrane Antigen-Targeting Radioligands in the Salivary Glands.

Background: Prostate specific membrane antigen (PSMA)-targeted radioligand therapies represent a highly effective treatment for metastatic prostate cancer. However, high and sustain uptake of PSMA-ligands in the salivary glands led to dose limiting dry mouth (xerostomia), especially with α-emitters. The expression of PSMA and histologic analysis couldn't directly explain the toxicity, suggesting a potential off-target mediator for uptake. In this study, we set out to search for possible off-target non-PSMA protein(s) in the salivary glands. Methods: A machine-learning based quantitative structure activity relationship (QSAR) model was built for seeking the possible off-target(s). The resulting target candidates from the model prediction were subjected to further analysis for salivary protein expression and structural homology at key regions required for PSMA-ligand binding. Furthermore, cellular binding assays were performed utilizing multiple cell lines with high expression of the candidate proteins and low expression of PSMA. Finally, PSMA knockout (PSMA-/-) mice were scanned by small animal PET/MR using [68Ga]Ga-PSMA-11 for in-vivo validation. Results: The screening of the trained QSAR model did not yield a solid off-target protein, which was corroborated in part by cellular binding assays. Imaging using PSMA-/- mice further demonstrated markedly reduced PSMA-radioligand uptake in the salivary glands. Conclusion: Uptake of the PSMA-targeted radioligands in the salivary glands remains primarily PSMA-mediated. Further investigations are needed to illustrate a seemingly different process of uptake and retention in the salivary glands than that in prostate cancer.

De Novo Transcriptome Profiling of Mustard Aphid (Lipaphis erysimi) and Differential Expression of Transcripts Associated with Feeding and Non-Feeding Conditions and Developmental Stages.

Lipaphis erysimi is a specialist aphid of the Indian subcontinent that causes significant yield losses in oilseed Brassicas. Several aphid genes have been used as preferred targets in RNAi-based transgenic plants for aphid resistance. In order to enhance the repertoire of potential target genes for aphid control and to identify the genes associated with aphid feeding and development, we performed a two-way comparative study of differential gene expression profiles between (i) feeding and non-feeding adults and (ii) adult and nymph developmental stages of L. erysimi. De novo RNA-seq of aphids using Illumina technology generated a final transcriptome comprising 52,652 transcripts. Potential transcripts for host selection, detoxification, salivary proteins and effectors, molecular chaperones and developmental genes were identified. Differential gene expression studies identified variations in the expression of 1502 transcripts between feeding and non-feeding adults and 906 transcripts between nymphs and adults. These data were used to identify novel target genes for RNAi-based aphid control and facilitate further studies on the molecular basis of aphid feeding and development.

Efficacy of Pomegranate Peel Extract Mouthwash on Gingivitis and C-reactive protein

Background and objective: Gingivitis is characterized as the world’s most predominant inflammatory periodontal disease. Healthy mouth and teeth are obtained by brushing and uses mouthwash. And because of the side effects of chlorhexidine, pomegranate peel extract mouthwash used alternative which are thought to have anti-inflammatory effect. The aim of this study is to prepare a herbal mouthwash and to evaluate the efficacy of pomegranate peel extract mouthwash on plaque index, gingival index, and C-reactive protein on moderate gingivitis patients. Method: this study is a clinical crossover design study, which consists of 25 volunteers with moderate gingivitis, who visited Duhok Dental Training Center. This study started from December 2022 to March 2023. Plaque and gingival index with a sample of saliva for C-reactive protein measuring were taken as a baseline before each mouth wash and after that, the pomegranate peel extract mouthwash was used for two weeks, then three weeks wash out between them, then chlorhexidine mouth wash was used for two weeks (crossover method). All saliva samples were analyzed using (CRP ELISA Test). Results: Twenty-five patients who used pomegranate peel extract mouthwash showed a significant reduction after two weeks used (CRP=162.28, GI=0.54, PI=0.82) and p value (<0.0001) in mean C-reactive protein, gingival index, and plaque index from baseline which was (CRP=669.78, GI=1.88, PI=2.11). Conclusion: Pomegranate peel extract mouthwash had been shown effective against moderate gingivitis in adult patients with no systemic diseases through lowering in mean salivary C-reactive protein, gingival index, and plaque index.

Virus-like particle-based vaccines targeting the Anopheles mosquito salivary protein, TRIO.

Malaria is a highly lethal infectious disease caused by Plasmodium parasites. These parasites are transmitted to vertebrate hosts when mosquitoes of the Anopheles genus probe for a blood meal. Sporozoites, the infectious stage of Plasmodium , transit to the liver within hours of injection into the dermis. Vaccine efforts are hindered by the complexity of the parasite's lifecycle and the speed at which the infection is established in the liver. In an effort to enhance immunity against Plasmodium , we produced a virus-like particle (VLP)-based vaccine displaying an epitope of TRIO, an Anopheles salivary protein which has been shown to enhance mobility and dispersal of sporozoites in the dermis. Previous work demonstrated that passive immunization with TRIO offered protection from liver infection and acted synergistically with a Plasmodium targeted vaccine. Immunization of mice with TRIO VLPs resulted in high-titer and long-lasting antibody responses that did not significantly drop for over 18 months post-immunization. TRIO VLPs were similarly immunogenic when combined with an anti-malaria vaccine targeting the L9 epitope of the Plasmodium falciparum circumsporozoite protein.However, when used in a malaria challenge mouse model, TRIO VLPs only provided modest protection from infection and did not boost the protection provided by L9 VLPs.

Knockdown of Fzr inhibited the growth of Nilaparvata lugens by blocking endocycle.

The endocycle can generate cells referred to as 'polyploid'. Fizzy-related protein (Fzr) plays an important role in driving the mitosis-to-endocycle transition. The brown planthopper (BPH), Nilaparvata lugens (Stål), a serious insect pest, feeds exclusively on rice. However, polyploidy and its regulatory mechanisms are poorly understood in BPH. Here, we found that the ploidy levels of follicles H (FH) and accessory gland (AG) significantly increased with BPH age when examining the polyploidy of FH and AG of salivary glands. Fzr was identified as an important regulator for polyploidy in BPH salivary gland. Knockdown of Fzr resulted in a decrease in cell size and DNA content in nymph salivary glands. Fzr knockdown transcriptionally upregulated cyclin-dependent kinase 1 (CDK1), CDK2, cyclin A (CycA) and CycB, and downregulated CycD, CycE, Myc and mini-chromosome maintenance protein 2-7 (MCM2-7). Phenotypically, Fzr knockdown significantly suppressed salivary protein production, feeding and survival in BPH nymphs. Our results show that BPH salivary glands exhibit obvious polyploidy, and Fzr positively regulates the endocycle in nymph salivary gland. These findings provide clues for the study of the regulatory mechanisms of insect polyploidy. © 2024 Society of Chemical Industry.

The down-regulation of salivary protein gene expression by etofenprox partially contributed to reducing the risk of increased fecundity in the brown planthopper

Etofenprox is a pyrethroid insecticide that acts on the nervous system of insects. Due to its low toxicity to aquatic animals, it is permitted for use in controlling insect pests in rice fields. The brown planthopper (BPH), Nilaparvata lugens, a significant piercing-sucking pest feeding on rice exclusively, secretes various salivary components when feeding. Salivary proteins are essential for BPH feeding, but their response to etofenprox is not well understood. The application of etofenprox down-regulated the expression of 21 salivary protein genes, among which 9 genes (NlShpa, Salivap 3, CA, NlSEF1, Nl12, NlHSC70–3, NlSP1, NlG14, and NlDNAJB9) showed significant differences. Most differentially expressed genes are found important for BPH physiological processes, except Nl12. Here we found that silencing Nl12 impeded ovary development, thereby inhibiting oocyte formation. The potential explanation was that Nl12 was highly expressed in both salivary gland and ovary, and the ovary development abnormality may be due to the direct effect from expression reduction in ovary and/or indirect influence from expression reduction in salivary gland. Altogether, our findings provide a new insight into the mechanism of action of etofenprox on insect pests and explain part of the reason why etofenprox does not stimulate reproduction in BPH.

Identification of N-linked glycans recognized by WGA in saliva from patients with non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related deaths. Saliva diagnosis is an essential approach for clinical applications owing to its noninvasive and material-rich features. The purpose of this study was to investigate differences in wheat germ agglutinin (WGA)-based recognition of salivary protein N-linked glycan profiles to distinguish non-small cell lung cancer (NSCLC) patients from controls. We used WGA-magnetic particle conjugates to isolate glycoproteins in the pooled saliva of healthy volunteers (HV, n = 35), patients with benign pulmonary disease (BPD, n = 35), lung adenocarcinoma (ADC, n = 35), and squamous cell carcinoma (SCC, n = 35), following to release the N-linked glycans from the isolated proteins with PNGase F, and further identified and annotated the released glycans by MALDI-TOF/TOF-MS, respectively. The results showed that 34, 35, 39, and 44 N-glycans recognized by WGA were identified and annotated from pooled saliva samples of HV, BPD, ADC, and SCC, respectively. Furthermore, the proportion of N-glycans recognized by WGA in BPD (81.2 %), ADC (90.1 %), and SCC (88.7 %), increased compared to HV (71.9 %). Two N-glycan peaks (m/z 2286.799, and 3399.211) specifically recognized by WGA were present only in NSCLC. These findings suggest that altered salivary glycopatterns such as sialic acids and GlcNAc containing N-glycans recognized by WGA might serve as potential personalized biomarkers for the diagnosis of NSCLC patients.

Iguratimod suppresses plasma cell differentiation and ameliorates experimental Sjögren's syndrome in mice by promoting TEC kinase degradation.

Primary Sjögren's syndrome (pSS) is a chronic inflammatory autoimmune disease with an unclear pathogenesis, and there is currently no approved drug for the treatment of this disease. Iguratimod, as a novel clinical anti-rheumatic drug in China and Japan, has shown remarkable efficacy in improving the symptoms of patients with pSS in clinical studies. In this study we investigated the mechanisms underlying the therapeutic effect of iguratimod in the treatment of pSS. Experimental Sjögren's syndrome (ESS) model was established in female mice by immunizing with salivary gland protein. After immunization, ESS mice were orally treated with iguratimod (10, 30, 100 mg·kg-1·d-1) or hydroxychloroquine (50 mg·kg-1·d-1) for 70 days. We showed that iguratimod administration dose-dependently increased saliva secretion, and ameliorated ESS development by predominantly inhibiting B cells activation and plasma cell differentiation. Iguratimod (30 and 100 mg·kg-1·d-1) was more effective than hydroxychloroquine (50 mg·kg-1·d-1). When the potential target of iguratimod was searched, we found that iguratimod bound to TEC kinase and promoted its degradation through the autophagy-lysosome pathway in BAFF-activated B cells, thereby directly inhibiting TEC-regulated B cells function, suggesting that the action mode of iguratimod on TEC was different from that of conventional kinase inhibitors. In addition, we found a crucial role of TEC overexpression in plasma cells of patients with pSS. Together, we demonstrate that iguratimod effectively ameliorates ESS via its unique suppression of TEC function, which will be helpful for its clinical application. Targeting TEC kinase, a new regulatory factor for B cells, may be a promising therapeutic option.

Fermented food consumption modulates the oral microbiota

Fermented food consumption is recommended for health and environmental purposes. While it is known to impact gut microbiota, further investigation is needed to establish connections with the oral microbiota. For this purpose, we investigated the effect of daily consumption of a model cheese containing 3 Lactic Acid Bacteria (LAB) species on the oral microbiota of rats following a 3-week diet. Cheese consumption transiently modifies the oral microbiota and leads to a transient persistence of LAB in the oral cavity of 1/3 of the animals. The origin of this variability was partly explained by an overrepresentation of salivary proteins involved in the response to oxidative stress in animals without LAB persistence. These findings highlight the significance of fermented foods in shaping the diversity of the oral microbiota. Additionally, they suggest that variations in the salivary proteome among individuals may influence the permissiveness of the oral microbiota towards exogenous microorganisms.

Salivary C-reactive protein exhibits a diurnal pattern and relates to biobehavioral health in military men

C-reactive protein is a systemic inflammatory biomarker that is positively associated with the development of disease. Salivary C-reactive protein (sCRP) has previously been reported to have a diurnal rhythm with higher levels upon awakening and lower levels thereafter. The aims of this study were to evaluate the stability of sCRP across two days, characterize the daily sCRP pattern, compute morning sCRP parameters, and evaluate associations with biobehavioral health in US Navy Explosive Ordnance Disposal (EOD) technicians. Seventy male EOD technicians (age = 34.9 ± 6.5 years) participated in this study, which included a tablet-based survey, measures of health and fitness, and saliva collection. In a free-living setting, participants self-collected saliva on 2 consecutive days at WAKE, WAKE+30, WAKE+60, 4p.m., and 9p.m., for a total of 10 samples. Parameters (e.g., area under the curve) were computed to characterize the morning sCRP magnitude and pattern. Pearson product-moment correlation analyses were used to assess the stability of sCRP samples and parameters across the study period and to examine associations with biobehavioral health. Average sCRP concentrations for the 2-day period were evaluated using an analysis of variance with repeated measures. The stabilities between corresponding time points on Days 1 and 2 were very high (rs = 0.87–.94, all ps ≤ 0.001). sCRP concentrations were highest at WAKE, decreased by 73.6 % at WAKE+30, and then plateaued for the rest of the day. Parameter stabilities were good to excellent (rs = 0.77–.98, all ps ≤ 0.001). We also observed associations between sCRP parameters, self-reported health behaviors, and objective measures of health and fitness. In this study of a military population, we characterized sCRP as diurnal with robust stability across 2 consecutive days, which demonstrates the feasibility of sCRP as a biomarker. These results have significant implications for study methodology and for using sCRP as a marker of dysfunction or disease.