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Persistent malodor affects many people worldwide and is usually associated with poor dental hygiene. This pilot trial aimed to determine whether proper dental hygiene (DH) and a probiotic dietary supplement support oral health in volunteers with persistent malodor. Volunteers (n = 35) were randomly assigned to the probiotic or placebo cohort. The probiotic cohort (n = 20) brushed and flossed their teeth twice daily and used probiotics for 30 days; the placebo cohort (n = 15) followed the same hygiene practices and used the placebo. The intervention phase was followed by a 30-day follow-up period. Measured outcomes were malodor and tongue-coating scores, probiotic DNA levels, salivary cytokines, and salivary pH. DH and probiotics significantly decreased malodor (~50% during intervention) and tongue coating scores (~45% during intervention). These changes remained through the course of the trial. The probiotic DNA levels increased in the probiotic cohort and dropped in the placebo cohort after the intervention started. The malodor moderately correlated with the tongue coating P. acidilactici level. The addition of probiotics increased IL-10 levels during the intervention and decreased IL-8, TNF-α, and IL-6 by the end of the study. People with malodor may benefit from using DH and probiotics. Additional trials are needed to definitively establish the benefits of probiotic dietary supplements. [ABSTRACT FROM AUTHOR]

Chronic stress and elevated cortisol are associated with adverse metabolic profiles and lifestyle patterns, systemic low-grade inflammation, and increased chronic disease risk; however, it is less clear how the degree of cortisol fluctuations impacts these parameters. Adult men and women (18-70y) were recruited to participate in a 5-day observational study, in which they underwent a baseline health and body composition assessment, completed 5-day diet, exercise, and stress records, and provided saliva samples in the morning, afternoon, and evening to measure fluctuations in cortisol, interleukin-1β (IL-1β), and IL-6. Degree of cortisol variability over the 5-day period (highest cortisol measure - lowest cortisol measure) was used to classify subjects into high (n = 9) and low (n = 9) cortisol fluctuation groups. Participants with greater fluctuations in salivary cortisol had higher salivary cortisol concentrations on average, which was attributed to higher maximal and morning cortisol. A greater proportion of individuals with higher cortisol flux worked in first responder/emergency professions, and exhibited minimal dietary pattern differences compared to those with low cortisol flux. While body fat percentage and mass positively correlated with minimum salivary cortisol measures, body composition and blood pressure did not differ between low vs. high salivary cortisol flux groups. Interestingly, we observed diurnal patterns of salivary IL-1β concentrations, with higher IL-1β in the morning, and greater afternoon IL-1β in the high cortisol flux group compared to the low cortisol flux group. Independent of cortisol flux, waking satiety and intake patterns of dietary nutrients and food groups/type differentially correlated with salivary cytokine concentrations in a time of day-dependent manner. Our findings suggest that greater fluctuations in cortisol are associated with distinct diurnal salivary cortisol and IL-1β concentrations but minimal lifestyle and dietary factors, whereas dietary patterns are strongly and differentially associated with salivary cytokine profiles.

Background: Oral mucositis is a common and distressing side effect of head and neck oncology treatment. Photobiomodulation therapy can be utilized to prevent and treat oral mucositis. Its impact on salivary cytokines has yet to be thoroughly investigated. This is the first systematic review aiming to evaluate the effect of photobiomodulation on salivary cytokines in patients undergoing anticancer treatment. Methods: Numerous data resources, from the Web of Science, Embase, ScienceDirect, PubMed, Cochrane Library, and Scopus were sought. Articles published up until February 2024 were included if they met the following inclusion criteria: clinical trials reporting the effect on salivary cytokines in patients undergoing anticancer therapy. The methodological quality was assessed using several appraisal tools. Results: Four studies were deemed eligible for inclusion. All the studies were conducted in Brazil and used an InGaAlP diode laser with a wavelength of 660 nm. The included studies had a relatively low risk of bias. The head and neck cancer patients' salivary cytokines that were assessed by the studies, along with photobiomodulation therapy, included IL-12p70, TNF-α, IL-6, IL-8, IL-10, CXCL8, and IL-1β. The results varied among the studies. Conclusions: Our results show that photobiomodulation demonstrated positive results for reducing the severity of OM in all the included studies. Among the examined salivary cytokines, IL-6 is the most relevant cytokine for oral mucositis development and severity. A variation in the cytokine levels between the studies was noted due to differences in the type of anticancer treatment and saliva sampling. [ABSTRACT FROM AUTHOR]

β-Thalassemia Major, a severe genetic blood disorder, necessitates lifelong blood transfusions and can lead to various complications, including oxidative stress and dental caries. This study aims to evaluate the salivary levels of cytokines Interleukin10 (IL-10) and Tumor Necrosis Factor-alpha (TNF-α) in pediatric βthalassemia Major patients and their association with dental caries. With 80 participants aged 8-12, split equally between patients and healthy controls, it found significantly higher cytokine levels in patients, indicating an altered immune response. Despite higher dental caries severity in patients, no significant correlation with cytokine levels was noted. The findings underscore the necessity for specialized dental care for β-thalassemia Major patients due to their increased risk of dental caries, highlighting the potential impact of their condition on oral health. [ABSTRACT FROM AUTHOR]

Abstract Purpose This study investigated the levels of salivary proinflammatory cytokines in the saliva of patients living with type II diabetes mellitus (DM) compared to those in healthy individuals three times: before tooth extraction and at 2 hours and 2 days after tooth extraction. Methods The study included 27 participants. Among them, 20 (n = 20; 74%) had type II DM, and seven (n = 7; 26%) were healthy control subjects. Saliva samples were collected at three time intervals: before tooth extraction and 2 hours and 2 days after tooth extraction. The salivary biomarkers were investigated using a Luminex multiplex assay. These salivary biomarkers included tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), interleukin 1-beta (IL-1β), and interferon-gamma (IFN-γ). Results At baseline, patients with type II DM had significantly lower levels of IL-1β (P = 0.016). Moreover, 2 hours after extraction, patients with type II DM had significantly lower levels of IL-1β and TNF-α than did healthy control subjects (P = 0.046 and P = 0.020, respectively). In addition, 2 days after tooth extraction, the DM group had significantly greater IL-6 levels (P = 0.010) than the control group. Conclusions In patients with type II DM, salivary proinflammatory biomarker levels are generally comparable or lower than those in healthy control subjects. Proinflammatory cytokines manifest differently in patients with type II DM after tooth extraction than in normal healthy individuals. There is generally a delayed early response of salivary proinflammatory markers in patients living with type II DM who undergo tooth extraction.

Persistent malodor affects many people worldwide and is usually associated with poor dental hygiene. This pilot trial aimed to determine whether proper dental hygiene (DH) and a probiotic dietary supplement support oral health in volunteers with persistent malodor. Volunteers (n = 35) were randomly assigned to the probiotic or placebo cohort. The probiotic cohort (n = 20) brushed and flossed their teeth twice daily and used probiotics for 30 days; the placebo cohort (n = 15) followed the same hygiene practices and used the placebo. The intervention phase was followed by a 30-day follow-up period. Measured outcomes were malodor and tongue-coating scores, probiotic DNA levels, salivary cytokines, and salivary pH. DH and probiotics significantly decreased malodor (~50% during intervention) and tongue coating scores (~45% during intervention). These changes remained through the course of the trial. The probiotic DNA levels increased in the probiotic cohort and dropped in the placebo cohort after the intervention started. The malodor moderately correlated with the tongue coating P. acidilactici level. The addition of probiotics increased IL-10 levels during the intervention and decreased IL-8, TNF-α, and IL-6 by the end of the study. People with malodor may benefit from using DH and probiotics. Additional trials are needed to definitively establish the benefits of probiotic dietary supplements.

Purpose: This study investigated the levels of salivary proinflammatory cytokines in the saliva of patients living with type II diabetes mellitus (DM) compared to those in healthy individuals three times: before tooth extraction and at 2 hours and 2 days after tooth extraction. Methods: The study included 27 participants. Among them, 20 (n = 20; 74%) had type II DM, and seven (n = 7; 26%) were healthy control subjects. Saliva samples were collected at three time intervals: before tooth extraction and 2 hours and 2 days after tooth extraction. The salivary biomarkers were investigated using a Luminex multiplex assay. These salivary biomarkers included tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), interleukin 1-beta (IL-1β), and interferon-gamma (IFN-γ). Results: At baseline, patients with type II DM had significantly lower levels of IL-1β (P = 0.016). Moreover, 2 hours after extraction, patients with type II DM had significantly lower levels of IL-1β and TNF-α than did healthy control subjects (P = 0.046 and P = 0.020, respectively). In addition, 2 days after tooth extraction, the DM group had significantly greater IL-6 levels (P = 0.010) than the control group. Conclusions: In patients with type II DM, salivary proinflammatory biomarker levels are generally comparable or lower than those in healthy control subjects. Proinflammatory cytokines manifest differently in patients with type II DM after tooth extraction than in normal healthy individuals. There is generally a delayed early response of salivary proinflammatory markers in patients living with type II DM who undergo tooth extraction. [ABSTRACT FROM AUTHOR]

The most prevalent form of leukocytes in human blood, neutrophils, is regarded as an essential part of the innate immune system and the body's 1st line of defense against foreign invaders. However, divergent opinions arise on the role of neutrophils in cancer, likely due to the occurrence of many neutrophil subsets. Several factors in the tumor microenvironment were found to modify the phenotype and function of neutrophils. Inhibitory cytokine production and recruitment of protumor immune cells to the tumor microenvironment are the reasons for immune suppression. Although some salivary cytokines were found to be increased in cancer patient's saliva, simultaneously, it was observed that those cytokines are high in other oral inflammatory conditions. So, it is challenging to distinguish at what level of expression those cytokines are involved in the neoplastic process. Therefore, the goal of this study is to provide a summary of the current information about the existence and presence of specific cytokines that impact cPMN and TAN and their potential activities in the context of healthy and cancer states so that we can relate to oPMN. [ABSTRACT FROM AUTHOR]

Objectives: To examine the effect of Nystatin oral rinse on oral Candida species and Streptococcus mutans carriage. Materials and methods: Twenty healthy adults with oral candidiasis participated in the single-arm clinical trial and received Nystatin oral rinse for 7 days, 4 applications/day, and 600,000 International Units/application. Demographic-socioeconomic-oral-medical conditions were obtained. Salivary and plaque Candida species and Streptococcus mutans were assessed at baseline and 1-week and 3-month follow-ups. Twenty-four salivary cytokines were assessed. Candida albicans isolates underwent Nystatin susceptibility test. Results: Half of participants (10/20) were free of salivary C. albicans after using Nystatin rinse. Salivary S. mutans was significantly reduced at 3-month follow-up (p < 0.05). Periodontal status reflected by bleeding-on-probing was significantly improved at 1-week and 3-month follow-ups (p < 0.05). Plaque accumulation was significantly reduced at 1-week follow-up (p < 0.05). Interestingly, the responses to Nystatin oral rinse were not associated with race, gender, age, oral hygiene practice, adherence to Nystatin rinse, or sweet consumption (p > 0.05). No C. albicans isolates were resistant to Nystatin. Furthermore, salivary cytokine eotaxin and fractalkine were significantly reduced at 3-month follow-up among participants who responded to Nystatin rinse (p < 0.05). Conclusions: The study results indicate that oral antifungal treatment had an effect on S. mutans salivary carriage. Future clinical trials are warranted to comprehensively assess the impact of antifungal treatment on the oral flora other than S. mutans and Candida. Clinical relevance: Due to the potential cariogenic role of oral Candida species, antifungal approaches shed new light on the prevention and management of dental caries from a fungal perspective. [ABSTRACT FROM AUTHOR]

Purpose: Experimental studies have shown that prolonged sitting for 2–8 h can cause changes to vascular and metabolic markers; the response of pro-inflammatory cytokines is relatively unexplored. The purpose of this study is to determine the response of interleukin-8 (IL-8) to prolonged and interrupted sitting. Methods: Healthy participants (n = 24, 21.1 years ± 2.2, 50% female) completed a prolonged sitting session (4 h) and an interrupted sitting session (4 h of sitting with 3 min of walking at 60%HRmax, every 30 min) in random order. Saliva and capillary plasma were collected at the beginning (T1) and at the end of each session (T2). Results: Salivary concentrations of IL-8 increased during the prolonged (T1 median: 22.09 pg/mL, T2 median: 86.18 pg/mL; p = < 0.01, ES − 0.55) and interrupted (T1 median: 22.09 pg/mL, T2 median: 51.99 pg/mL; p = 0.021, ES − 0.34) sessions; however, the increase during interrupted sitting was lower (PS median: 134.4%, range: − 43.96 to 1115.69 and IS median: 50.8%, range: − 75.5 to 356.35; p = 0.011, ES − 0.53). In the sub-sample of males, salivary IL-8 did not increase in the interrupted session (T1 median: 22.09, range: 3.496–699.12, and T2 median: 24.96, range: 5.11–533.5, p = > 0.05, ES − 0.16). No significant findings were observed for IL-8 in the plasma. Conclusion: Prolonged sitting appears to increase concentrations of the pro-inflammatory cytokine IL-8 while interrupting this sitting with short bouts of walking blunts this response. Sex appears to moderate this relationship; however, there appears to be a large amount of individual variability. [ABSTRACT FROM AUTHOR]

This research aimed to explore the relationship between tumor necrosis factor-α (TNF-α), Lactobacillus acidophilus (L. acidophilus), Lactobacillus gasseri (L. gasseri), obesity, and early childhood caries. After caries and obesity diagnosis based on the WHO criteria, 94 preschoolers were assessed. Unstimulated saliva was collected for analysis of TNF-α by the Milliplex system and for L. acidophilus and L. gasseri using real-time polymerase chain reaction (RT-PCR). In obese children, each unit increase in the body mass index (BMI), and the TNF-α levels was associated with a one-time increase in the number of decayed surfaces (p < 0.05). Meanwhile, in eutrophic preschoolers, the presence of L. gasseri and L. acidophilus was linked, respectively, to an increase of 3.04 and 1.59 times in the number of decayed surfaces (p < 0.05); in obese children, the presence of L. acidophilus was not significant (p > 0.05) and L. gasseri was shown as a possible protective indicator (RR:0.49–p < 0.05). In conclusion, TNF-α and BMI were connected to carious lesions only in obese preschoolers, suggesting that inflammation could be underscored when both pathologies are concomitant. The presence of both species of lactobacilli investigated was connected with early childhood caries in eutrophic children, whereas in obese children only L. gasseri was significant, and in an opposite way, reinforcing that obesity can modulate oral bacteria. [ABSTRACT FROM AUTHOR]

ABSTRACT The long-term exposure to enclosed environments may lead to chronic stress in crewmembers and affect their physical and mental state. Salivary microbiome and biomarkers of immune function are increasingly used in human health research. The “Lunar Palace 365” project, which was a 370-day, multicrew, enclosed experiment carried out in a ground-based bioregenerative life support system platform named Lunar Palace 1 (LP1). We investigated the temporal dynamics of the salivary microbiota and cytokines in the third phase of the “Lunar Palace 365” experiment, including 1 month before entering LP1 and 1 month after leaving Lp1. Results reveal no regular temporal change pattern in these parameters (highly abundant phyla and genera) during the experiment. Although the crewmembers’ oral microbiota temporally changed, it recovered quickly after the study subjects left the enclosed environment. The levels of IL-6, IL-10, and TNF-α in crewmembers’ saliva decreased after leaving the normal environment for the enclosed environment, indicating that their oral inflammatory response level was reduced. There were significant individual differences in crewmembers’ salivary microbiota, however, the shared living space reduced these differences. Moreover, air microbiota might have also played a significant role in reducing the individual differences. In summary, the enclosed environment did not result in persistent changes in human salivary microbiota and oral immunity. This study provides some insights for studying the effect of enclosed controlled environments on human immunity and microbiome. IMPORTANCE Long-term exposure to space environments may influence the human microbiome, the human immune system, and the intricate balance between the two, causing impaired immunity and increased disease susceptibility. It was previously believed that the main potential factors of long-term spaceflight on human health were microgravity and radiation. However, the effects of long-term enclosed environments on human health were unclear. Bioregenerative life support systems (BLSS) is a good experimental model for studying the effects of enclosed environments on human systemic microbiota and immune disorders. We monitored the microbiota and cytokines in the saliva of crewmembers before they entered BLSS, during their stay in BLSS, and after leaving BLSS. The results indicated long-term closed environment will not cause persistent changes in human salivary microbiota and immunity.

Background: Periodontal disease is an inflammatory, dysbiotic condition. Studies have shown that in the elderly, periodontal disease was associated with cognitive dysfunction and Alzheimer's disease. Objective: To investigate whether young healthy subjects with periodontal disease have lower cognition compared to those without periodontal disease. The salivary cytokines (IL-1β, TNF-α) levels in relation to cognition were also tested. Methods: In a monocenter, cross-sectional study, forty subjects [mean age (SD) = 34 (5) and 48% female] from western Romania were classified into periodontal disease conditions using radiographic assessment: 10 subjects had aggressive periodontitis (AGG_P), 20 chronic mild-moderate periodontitis (CR_P), and 10 no periodontitis (NL_P). Neuropsychological assessment performed by standardized neurologists and psychologist included Rey Auditory Verbal Learning Test (RAVLT), Montreal Cognitive Assessment test (MOCA), Mini-Mental State Examination (MMSE), and Prague tests. Salivary cytokines levels were determined by ELISA. Results: RAVLT and MOCA delayed recall scores were lower in AGG_P group compared to NL_P and CR_P. The learning curve was also different with subjects with AGG_P showing reduced learning performance. Contrary to our hypothesis, salivary IL-1β associated with immediate but not delayed cognitive scores. Conclusions: These results showed for the first time that subjects with AGG_P had cognitive dysfunction and IL-1β may play a role in this process. [ABSTRACT FROM AUTHOR]

Background: Research studies indicate that polycystic ovary syndrome (PCOS) may increase susceptibility to periodontal disease. The mechanisms that link both conditions are not entirely understood. Thus, the study aimed to investigate the impact of hormonal and metabolic disturbances on the gingival health and salivary levels of tumor necrosis factor (TNF-α), interleukin 1β (IL1-β), and interleukin 6 (IL-6) in adolescent girls with PCOS. Methods: Thirty-one patients with PCOS and twenty-eight healthy age-mates (as the control group) were enrolled in the study. Individuals with PCOS underwent blood tests for the determination of hormonal and metabolic parameters. Saliva samples were collected to measure salivary testosterone and proinflammatory cytokines in both studied groups. Calibrated dentist assessed oral hygiene and gingival health of all subjects. Results: Salivary testosterone was significantly higher in the study group (p = 0.0007). The groups did not differ significantly concerning periodontal parameters. Patients with PCOS revealed higher levels of salivary cytokines (p < 0.0001). Gingival index (GI) and the percentage of sites bleeding upon probing (BOP%) were positively correlated with the plaque index (PI) in both groups (rs ≥ 0.60, p < 0.001), and negatively correlated with salivary testosterone level in the PCOS group (rs = − 0.44, p = 0.0138 and rs = − 0.37, p = 0.0424, respectively). BOP% was also positively correlated with body mass index (BMI) in the control group (rs = 0.40, p = 0.0368) and index of insulin resistance (HOMA-IR) in the study group (rs = 0.48, p = 0.0068). Salivary testosterone was positively correlated with TNF-α in the control group (rs = 0.41, p = 0.0321), while in the study group, total testosterone (TT) was positively correlated with IL-6 (rs = 0.37, p = 0.0400) and free androgen index (FAI) with TNF-α (rs = 0.36, p = 0.0491). Conclusions: Gingival health of the examined population was associated primarily with oral hygiene and, to a lesser extent, with the hormonal and metabolic profile. Despite similar periodontal parameters in the both studied groups, patients with PCOS revealed significantly higher levels of proinflammatory cytokines in saliva, which might be the manifestation of the systemic low-grade inflammation associated with PCOS. [ABSTRACT FROM AUTHOR]

This research aimed to explore the relationship between tumor necrosis factor-α (TNF-α), Lactobacillus acidophilus (L. acidophilus), Lactobacillus gasseri (L. gasseri), obesity, and early childhood caries. After caries and obesity diagnosis based on the WHO criteria, 94 preschoolers were assessed. Unstimulated saliva was collected for analysis of TNF-α by the Milliplex system and for L. acidophilus and L. gasseri using real-time polymerase chain reaction (RT-PCR). In obese children, each unit increase in the body mass index (BMI), and the TNF-α levels was associated with a one-time increase in the number of decayed surfaces (p < 0.05). Meanwhile, in eutrophic preschoolers, the presence of L. gasseri and L. acidophilus was linked, respectively, to an increase of 3.04 and 1.59 times in the number of decayed surfaces (p < 0.05); in obese children, the presence of L. acidophilus was not significant (p > 0.05) and L. gasseri was shown as a possible protective indicator (RR:0.49–p < 0.05). In conclusion, TNF-α and BMI were connected to carious lesions only in obese preschoolers, suggesting that inflammation could be underscored when both pathologies are concomitant. The presence of both species of lactobacilli investigated was connected with early childhood caries in eutrophic children, whereas in obese children only L. gasseri was significant, and in an opposite way, reinforcing that obesity can modulate oral bacteria.

Using salivary inflammatory markers as a noninvasive biomonitoring technique within natural social contexts has become increasingly important to link social and biological responses. Many studies have associated circulating cytokines to distinct aspects of physical activity and social/emotional behavior; however, they have not been linked to success and failure in a naturalistic setting for military personnel performing tasks. In this study, salivary cytokines were studied in a group of fifteen Air Force Reserve Officers’ Training Corps (ROTC; 14 males, 1 female) subjects performing three mock hostage rescue missions, designed to prompt responses associated with baseline, success, and failure. Each subject completed the tasks of the mission individually and again in randomly assigned teams. Participants were outfitted via direct skin contact with comfortable external Zephyr™ sensors to monitor heart rate, breathing rate, and activity while completing each task. Saliva samples were collected before and after the completion of each mission, and cytokine levels were quantified using enzyme-labelled immunoassay (ELISA) beads. These biomarkers were used to describe the body’s immune response to success and failure when performing a mock rescue mission individually and in a team. All measured cytokine levels increased following failed missions performed individually, compared to cytokine levels associated with successful missions. When completing the tasks as a team, there were no significant differences in cytokine response between success and failure; however, being in a team stimulated an increased pre-mission cytokine response, suggesting the concept of teamwork and performing with peers for the first time had a more significant impact than the notion of failing. Additionally, none of the cytokines tested for individual missions correlated to physical activity markers (heart rate, breathing rate, activity) measured during performance. These results indicate a potentially new noninvasive method of determining social stress levels under taxing conditions.

Shift nurses are prone to sleep problems and impaired nighttime alertness, with risk for reduced health status plus decreased performance, handling errors, and workplace accidents. Attention to and improvements in the situation of shift nurses are urgent. Shimian granules (SMG), an improved formula of Jieyuanshen with liver qingre and yangxin tranquilizing effects, for more than a decade has been used in China as a herbal treatment of sleep disorders in clinical practice. However, clinical data on SMG have rarely been reported. This double-blinded, randomized, placebo-controlled, pilot clinical trial (ChiCTR-IOR-17013031) aimed to explore whether Shimian granules (SMG) improves sleep and affective state in shift nurses and in association with changes in concentrations of salivary cytokines. Fifty-three rotating-shift female nurses with a Pittsburgh Sleep Quality Index (PSQI) score ≥8 were orally treated with 10.0 g SMG or placebo 2 times daily (30 min after breakfast and 30 min before bed) for 1 month. The Insomnia Severity Index (ISI), a psychomotor vigilance task, Hospital Anxiety and Depression Scale (HADS-A/HADS-D), and levels of four salivary cytokines were evaluated by single time-of-day sampling at baseline and after 1 month of treatment. Significantly lower ISI, HADS, HADS-A, and HADS-D scores, but higher 1/mean reaction time (1/mRT) score, were found in shift nurses treated with SMG than in those who received placebo, and these effects were associated with changes in salivary melatonin, TNF, IL-1β, and IL-6 levels. These latter findings suggest melatonin, TNF, and IL-6 levels may be suitable biomarkers of ISI score in shift nurses, whereas TNF level may be a suitable biomarker of 1/mRT score and IL-6 level a suitable biomarker of HADS score in response to SMG treatment. The results of this pilot study suggest SMG can effectively improve sleep, alertness, plus anxiety and depression symptoms in shift nurses in association with changes in salivary cytokine levels. The results of this study provide an experimental basis for the evaluation of traditional Chinese medicines for the treatment of insomnia and underlying mechanisms of their actions that require detailed future exploration. [ABSTRACT FROM AUTHOR]

• We examined the short-term reliability and long-term stability of salivary immune markers. • All of the analytes achieved excellent short-term reliability by averaging four samples. • Long-term stability of the analytes was substantially improved by averaging two or more samples. • Salivary immune markers may thus be more stable than previously thought. Salivary markers of immune function are increasingly commonly used in studies of human health. Yet, few studies have examined the short-term or long-term reliability or stability of these biomarkers, making their measurement properties unclear. We addressed this issue in the present study by collecting two saliva samples, two hours apart, from 426 adolescent girls during a baseline laboratory visit. Then, eighteen months later, we collected the same samples again from a subset of these participants (n = 113). The correlations between the two samples collected at each session were generally high (mean r = 0.67). In contrast, although single saliva samples were only weakly correlated across 18 month (mean r s = 0.18), averaging the two quantifications within a session considerably improved the reliability (mean r = 0.27). In short, salivary immune markers exhibited strong short-term test-retest correlations, and averaging across multiple assessments notably improved long-term test-retest correlations. Additional research is needed to establish the health relevance and mechanisms underlying these potentially useful, non-invasive biomarkers. [ABSTRACT FROM AUTHOR]

Shift work is unavoidable in modern societies, but at the same time disrupts biological rhythms and contributes to social distress and disturbance of sleep, health and well-being of shift workers. Shift work has been associated with some chronic diseases in which a chronic inflammatory condition may play a role. However, few studies investigating the association of cytokine and other inflammation markers with shift workers have been published in recent years. In this study we evaluated the effects of permanent night work on the production of tumor necrosis factor (TNF), interleukin-1β (IL-1β), IL-6 and melatonin in saliva. Another aim was to demonstrate the benefit of the use of salivary cytokines for studies in chronobiology, since it is an easy and non-invasive method that allows for sampling at several times. Thirty-eight healthy male workers, being 21 day workers and 17 night workers, agreed to participate in this study. Sleep was evaluated by actigraphy and activity protocols. Saliva was collected during three workdays approximately at the middle of the work shift and at bed and wake times of the main sleep episode. Saliva samples were then analyzed by enzyme-linked immunosorbent assay to measure TNF, IL-1β, IL-6 and melatonin levels, and the results were submitted to non-parametric statistical analysis. The use of saliva instead of blood allowed for a greater number of samples from the same subjects, allowing identifying alterations in the daily production patterns of salivary cytokines TNF, IL-1β and IL-6 that probably are linked to night work. Salivary TNF and IL-1β levels were similar for day and night workers, with higher daily production after awakening, in the morning hours for day workers and in the afternoon for night workers. Both groups presented a significant daily variation pattern of these two cytokines. Day and night workers produced similar amounts of salivary IL-6. Nevertheless, the daily variation pattern observed among day workers, with a peak after awakening, was absent among night workers. Thus, in our study, night workers showed partially adjusted daily variation patterns for salivary TNF and IL-1β, not seen for salivary IL-6. Results for salivary IL-6 could be better explained as a consequence of circadian disruption due to permanent night work. Our results suggest that the whole circadian system, including clocks and pineal gland, is involved in regulating cytokine profile in shift workers and that a coordinated production of these cytokines, important for an adequate inflammatory response, could be disturbed by shift work. The distinct effects that shift work may have on different cytokines could give some cues about the mechanisms involved in this association. [ABSTRACT FROM AUTHOR]

About 50% of patients with cystic fibrosis (CF) have sinonasal complications, which include inferior turbinate hypertrophy (NTH) and/or nasal polyposis (NP), and different degrees of lung disease, which represents the main cause of mortality. Monitoring of sinonasal disease requires complex instrumental procedures, while monitoring of lung inflammation requires invasive collection of bronchoalveolar lavage fluid. The aim of this study was to investigate the associations between salivary cytokines levels and CF-related airway diseases. Salivary biochemical parameters and cytokines, i.e., interleukin-6 (IL-6), IL-8, and tumor necrosis factor alpha (TNF-α), were analyzed in resting saliva from healthy subjects and patients with CF. Patients with CF showed significantly higher levels of salivary chloride, IL-6, IL-8, and TNF-α and lower calcium levels than healthy subjects. Among patients with CF, IL-6 and IL-8 were significantly higher in patients with NTH, while TNF-α was significantly lower in patients with NP. A decreasing trend of TNF-α in patients with severe lung disease was also observed. On the other hand, we did not find significant correlation between cytokine levels and Pseudomonas aeruginosa or Stenotrophomonas maltophilia colonization. These preliminary results suggest that salivary IL-6 and IL-8 levels increase during the acute phase of sinonasal disease (i.e., NTH), while the end stages of pulmonary disease and sinonasal disease (i.e., NP) show decreased TNF-α levels.

Abstract: While the presence of multiple systemic steroids, amines and peptides in saliva has been reported, other hormones of the circulation do not appear in saliva. Substances present within saliva may be classified in different groups: first, those which passively display blood plasma concentrations and constitute a promising alternative to evaluate certain systemic parameters. Second, molecules which seem to play a more active, regulatory role within the upper gastrointestinal tract. Concerning the latter, a growing awareness, especially with regards to salivary peptides has been established. Up to now, understanding the distinct effects of salivary peptides known so far is in its infancy. Various publications, however, emphasize important effects of their presence. Salivary peptides can influence inflammatory processes and cell proliferation in epithelia of the upper digestive tract. These include transforming growth factors (TGFs), epidermal growth factors (EGFs), vascular endothelial growth factors (VEGFs) as well as amines such as melatonin. Of those, candidate cytokines like interleukin 8, tumor necrosis factors (TNFs) and leptin are involved in neoplastic activities of salivary glands and the oral cavity. The exact mechanisms of action are not yet completely understood, but their presence can be utilized for diagnostic purposes. Salivary gland tumors in patients may, in certain circumstances, be identified by saliva diagnostics. Saliva samples of the concerned patients, for instance, reveal significantly higher leptin concentrations than those of healthy individuals. Numerous studies postulate that, beside single indicators, the establishment of salivary hormone profiles may assist clinicians and researchers in detecting tumors and other pathologies of the oral cavity, including adjacent tissues, with high sensitivity and specificity. [Copyright &y& Elsevier]

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The long-term exposure to enclosed environments may lead to chronic stress in crewmembers and affect their physical and mental state. Salivary microbiome and biomarkers of immune function are increasingly used in human health research. The "Lunar Palace 365" project, which was a 370-day, multicrew, enclosed experiment carried out in a ground-based bioregenerative life support system platform named Lunar Palace 1 (LP1). We investigated the temporal dynamics of the salivary microbiota and cytokines in the third phase of the "Lunar Palace 365" experiment, including 1 month before entering LP1 and 1 month after leaving Lp1. Results reveal no regular temporal change pattern in these parameters (highly abundant phyla and genera) during the experiment. Although the crewmembers' oral microbiota temporally changed, it recovered quickly after the study subjects left the enclosed environment. The levels of IL-6, IL-10, and TNF-α in crewmembers' saliva decreased after leaving the normal environment for the enclosed environment, indicating that their oral inflammatory response level was reduced. There were significant individual differences in crewmembers' salivary microbiota, however, the shared living space reduced these differences. Moreover, air microbiota might have also played a significant role in reducing the individual differences. In summary, the enclosed environment did not result in persistent changes in human salivary microbiota and oral immunity. This study provides some insights for studying the effect of enclosed controlled environments on human immunity and microbiome. IMPORTANCE Long-term exposure to space environments may influence the human microbiome, the human immune system, and the intricate balance between the two, causing impaired immunity and increased disease susceptibility. It was previously believed that the main potential factors of long-term spaceflight on human health were microgravity and radiation. However, the effects of long-term enclosed environments on human health were unclear. Bioregenerative life support systems (BLSS) is a good experimental model for studying the effects of enclosed environments on human systemic microbiota and immune disorders. We monitored the microbiota and cytokines in the saliva of crewmembers before they entered BLSS, during their stay in BLSS, and after leaving BLSS. The results indicated long-term closed environment will not cause persistent changes in human salivary microbiota and immunity.

Periodontitis is a chronic multifactorial inflammatory disease that leads to the loss of supportive tissues around the teeth with gradual deterioration of masticatory function and esthetics, resulting eventually in the decrease of the life quality. Host immune response triggered by bacterial biofilm is responsible for the chronic periodontal inflammation and ongoing tissue loss. Omega-3 polyunsaturated fatty acids (PUFA) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anti-inflammatory properties, thus may be used for the treatment of chronic inflammatory diseases. In this study, we aimed to evaluate the effect of dietary supplementation with omega-3 PUFA in the patients with stage III and IV periodontitis. Thirty otherwise healthy patients were treated with scaling and root planning (SRP). In the test group (n = 16), patients were additionally supplemented with 2.6 g of EPA and 1.8 g of DHA. In the control group (n = 14), patients received only SRP. Periodontal examination was performed at baseline and three months following initial therapy. Salivary samples were taken twice at baseline and at the end of the experiment. We found that there was a statistically significant reduction in the bleeding on probing (BOP) and improvement of clinical attachment loss (CAL) at three months in the test group compared to the control group. Moreover, a statistically significant higher percentage of closed pockets (probing depth ≤ 4 mm without BOP) was achieved in the test group vs. control group after three months of treatment. Accordingly, the levels of pro-inflammatory cytokines/chemokines interleukin (IL)-8 and IL-17 were markedly lower, while the level of anti-inflammatory IL-10 was significantly higher in the salivary samples of the patients supplemented with omega-3 PUFA at three months in comparison to the patients treated with SRP alone. Our findings demonstrate that dietary intervention with high-dose of omega-3 PUFA during non-surgical therapy may have potential benefits in the management of periodontitis. [ABSTRACT FROM AUTHOR]

About 50% of patients with cystic fibrosis (CF) have sinonasal complications, which include inferior turbinate hypertrophy (NTH) and/or nasal polyposis (NP), and different degrees of lung disease, which represents the main cause of mortality. Monitoring of sinonasal disease requires complex instrumental procedures, while monitoring of lung inflammation requires invasive collection of bronchoalveolar lavage fluid. The aim of this study was to investigate the associations between salivary cytokines levels and CF-related airway diseases. Salivary biochemical parameters and cytokines, i.e., interleukin-6 (IL-6), IL-8, and tumor necrosis factor alpha (TNF-α), were analyzed in resting saliva from healthy subjects and patients with CF. Patients with CF showed significantly higher levels of salivary chloride, IL-6, IL-8, and TNF-α and lower calcium levels than healthy subjects. Among patients with CF, IL-6 and IL-8 were significantly higher in patients with NTH, while TNF-α was significantly lower in patients with NP. A decreasing trend of TNF-α in patients with severe lung disease was also observed. On the other hand, we did not find significant correlation between cytokine levels and Pseudomonas aeruginosa or Stenotrophomonas maltophilia colonization. These preliminary results suggest that salivary IL-6 and IL-8 levels increase during the acute phase of sinonasal disease (i.e., NTH), while the end stages of pulmonary disease and sinonasal disease (i.e., NP) show decreased TNF-α levels. [ABSTRACT FROM AUTHOR]

It is well known that cytokines are involved in the homeostasis of oral cavity and that altered levels of either serum and/or salivary cytokines have been found in certain oral/systemic diseases. So far, cytokines in connection with xerostomia have been investigated in patients with Sjögren's syndrome. We wanted to find out whether drugs themselves influence salivary glands, which would result in altered cytokine level or whether xerostomia itself of different causes leads to the changes in salivary cytokine levels. Therefore, the aim of this study was to evaluate levels of salivary interleukin-6 (IL-6) and tumor necrosis factor (TNF)- α in 30 patients with drug-induced xerostomia, age range 29–84 and mean 63.9 years. Control group consisted of 30 healthy participants, age range 30–82 years and mean age 65.2 years. Enzyme-linked immunoassay was performed on commercially available kits. Statistical analysis was performed by use of Student's test. No significant differences in salivary IL-6 and TNF- α between patients with drug-induced xerostomia when compared with the healthy controls were found ( P < 0.05). We might conclude that drugs do not induce damage to the salivary glands which could be seen in altered salivary IL-6 and TNF- α levels and that xerostomia itself, induced by drugs does not alter levels of the investigated salivary cytokines. [ABSTRACT FROM AUTHOR]

Background: Recurrent apthous ulceration (RAU) is a well known oral disease which seems to be mediated principally by the immune system. However, it is still a matter of debate which part of the immune system is implicated in its pathogenesis as a reaction to the still unknown antigen. The aim of this study was to evaluate salivary cytokines, interleukin (IL)-6, and tumor necrosis factor (TNF)- α. Methods: In 26 patients with minor RAU, age range of 23–49 years (mean 27.3 years), during both the acute phase and remission and in 26 healthy controls, age range of 22–64 years (mean 30.1 years), salivary IL-6 and TNF- α levels were determined by use of enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed by use of descriptive statistics. Results: Significant differences in salivary TNF- α between healthy controls and patients with acute RAU and during the remission period were found ( P < 0.001) as well as between patients with acute RAU and those during the remission period ( P < 0.001). No differences in salivary IL-6 between all three groups could be found. Conclusions: We might conclude that elevated salivary TNF- α levels during acute RAU and especially during the remission period are of importance in RAU, whereas salivary IL-6 levels seem not to play a role in the RAU disease. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is characterized by neurodevelopmental disorders and alterations in immune function and cytokine levels. The aim of this study is to determine the salivary levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor α (TNFα), monocyte chemoattractant protein-1 (MCP-1), Regulated on Activation, Normal T-cell Expressed and Secreted (RANTES), and Eotaxin in children with ASD and in healthy controlsto assess their predictive potential. We explored correlations between the cytokine levels and the neurodevelopmental disorders related to ASD. The study comprised 19 children with ASD and 19 typically developing (TD) ones. We analyzed salivary levels of IL-1β, IL-6, IL-8, TNFα, MCP-1, RANTES, and eotaxin on Luminex with custom-designed 7-plex kits. The level of RANTES in ASD children was significantly lower than those of TD. In TDs, the salivary levels of IL-1β, MCP-1, and TNFα correlated positively with age. In ASD, the cytokine levels did not correlate with age. There were statistically significant differences between the RANTES level and aggression and gait disturbances, between IL-8 level and fixations/stimulations, and between IL-1β level and no active speech. The levels of the cytokine detected can manifest both systemic and local changes related to ASD. The cytokine pattern cannot be used as a sole ASD predictor, but the salivary levels may be helpful in categorizing the ASD subtype.

Using salivary inflammatory markers as a noninvasive biomonitoring technique within natural social contexts has become increasingly important to link social and biological responses. Many studies have associated circulating cytokines to distinct aspects of physical activity and social/emotional behavior; however, they have not been linked to success and failure in a naturalistic setting for military personnel performing tasks. In this study, salivary cytokines were studied in a group of fifteen Air Force Reserve Officers' Training Corps (ROTC; 14 males, 1 female) subjects performing three mock hostage rescue missions, designed to prompt responses associated with baseline, success, and failure. Each subject completed the tasks of the mission individually and again in randomly assigned teams. Participants were outfitted via direct skin contact with comfortable external Zephyr™ sensors to monitor heart rate, breathing rate, and activity while completing each task. Saliva samples were collected before and after the completion of each mission, and cytokine levels were quantified using enzyme-labelled immunoassay (ELISA) beads. These biomarkers were used to describe the body's immune response to success and failure when performing a mock rescue mission individually and in a team. All measured cytokine levels increased following failed missions performed individually, compared to cytokine levels associated with successful missions. When completing the tasks as a team, there were no significant differences in cytokine response between success and failure; however, being in a team stimulated an increased pre-mission cytokine response, suggesting the concept of teamwork and performing with peers for the first time had a more significant impact than the notion of failing. Additionally, none of the cytokines tested for individual missions correlated to physical activity markers (heart rate, breathing rate, activity) measured during performance. These results indicate a potentially new noninvasive method of determining social stress levels under taxing conditions., Competing Interests: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article. This study was funded by the 10.13039/100000185Defense Advanced Research Projects Agency (DARPA, United States, W911NF-12-0165) and 10.13039/100000002NIH (United States, P20GM103434) to the West Viginia Institutional Development Award (IDeA) Networks of Biomedical Research Excellence (INBRE)., (© 2020 The Authors.)

Objective: To examine the associations of psychological strains, salivary biomarkers, and coronary heart disease (CHD) risks in hurricane survivors 2 years after Hurricane Ike in the United States., Background: Hurricane survivors often suffer from long-lasting posttraumatic stress disorder (PTSD) and other forms of psychological strain related to surviving a natural disaster and dealing with its aftermath. Psychological strains may be associated with biomarkers, which, in turn, may be associated with a higher incidence of CHD risks., Methods: Structured interviews were conducted with 19 hurricane survivors to assess psychological strains (PTSD, perceived stress, depression, and anxiety) and measure CHD risks. Saliva samples were collected by the passive drool method and analyzed for inflammatory cytokine (interleukin [IL]-1β, IL-6, and IL-10) and chemokine (monocyte chemotactic protein [MCP]-1) biomarkers., Results: The salivary level of MCP-1 was significantly associated with PTSD symptoms, depression (both p < .01), and anxiety (p < .05). There were significant associations between anxiety and hypertension (p < .01), perceived stress and blood glucose level (p < .05), and perceived stress and obesity (p < .05)., Conclusion: Our findings that long-lasting psychological strains are associated with major CHD risks and salivary MCP-1 levels suggest that the mechanism by which such strains play a role in the development of CHD involves recruitment of monocyte cells in response to chronic endothelial inflammation. Further studies are needed to advance our understanding of the underlying mechanisms by which the PTSD and other psychological strains contribute to the development of CHD., (© The Author(s) 2014.)