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This review is focused on the effects of lingonberry (Vaccinium vitis-idaea L.) fruit phenolic compounds in human in vitro cells and in vivo clinical studies. Studies with lingonberries, lingonberry juice/lingonberry nectar/fermented lingonberry juice, and phenolic fractions with active molecules are reviewed. Lingonberry's bioactive substances have a diverse range of antimicrobial, anti-inflammatory, antiproteolytic, anticancer, and antioxidant properties. Fermentation of lingonberries and modulation of the dysbiotic microbiome to a more symbiotic composition by favoring the growth of lactobacilli and inhibiting the growth of human opportunistic pathogens are discussed. Research results suggest that more studies on humans are needed. [ABSTRACT FROM AUTHOR]

Objective: The aim was to profile serum and salivary levels of active‐matrix metalloproteinase (aMMP)‐8, tissue inhibitor MMP (TIMP)‐1, aMMP‐8/TIMP‐1 ratio, total MMP (tMMP)‐9, tMMP‐9/TIMP‐1 ratio, myeloperoxidase (MPO), and human neutrophil elastase (HNE) in periodontitis and rheumatoid arthritis (RA). Materials and Methods: Rheumatoid arthritis patients with periodontitis (RA + P, n = 26), periodontally healthy RA patients (RA, n = 23), systemically healthy periodontitis patients (P, n = 24), and controls (C, n = 24) were included. aMMP‐8 levels were determined by a time‐resolved immunofluorescence assay (IFMA), TIMP‐1, tMMP‐9, MPO, and HNE levels were measured by enzyme‐linked immunosorbent (ELISA) assays. Results: Higher salivary aMMP‐8 (p < 0.001), aMMP‐8/TIMP‐1 ratio (p = 0.043), tMMP‐9 (p = 0.011), tMMP‐9/TIMP‐1 ratio (p = 0.022), MPO (p = 0.026) and HNE (p < 0.001) levels were detected in P relative to the controls. Salivary TIMP‐1 was increased in RA patients regardless of periodontal status (RA + P vs. P: p = 0.038; RA vs. C: p = 0.020). Serum neutrophil proteases were increased in RA groups (RA + P, RA) compared to systemically healthy groups (P, C) (p < 0.05). Conclusions: Serum levels of neutrophil proteases were increased in RA study groups; however rheumatologic status seemingly does not affect salivary levels of these proteins. [ABSTRACT FROM AUTHOR]

Objectives: This study examines the associations of active matrix metalloproteinase‐8 (aMMP‐8) point‐of‐care immunotest (Periosafe) outcomes with oral health of patients with haemato‐oncologic diseases. Methods: Adult patients diagnosed with haematological diseases aimed to be treated with haematopoietic stem cell transplantation (HSCT) between 2018 and 2019 were included in the study. Clinical and radiological dental examination were taken immediately prior to transplantation. The presence of oral foci of infections, caries or periodontitis was examined and compared with the outcomes of aMMP‐8 immunotest. Results: Acute oral infection foci were present in 11.9%, chronic in 44.1% and periodontitis in 42.0% of the 143 subjects. aMMP‐8 immunotest was positive in 13.3% of all the 143 subjects. Among subjects with periodontitis (n = 60), the aMMP‐8 immunotest was also positive in 13.3% of these subjects. However, the subjects with positive aMMP‐8 immunotest (n = 19) had more often acute or chronic infection foci and more than one of the examined dental treatment needs compared with subjects with negative immunotest (all p < 0.05). There were no differences in age, sex, hyposalivation, DMFT‐index values nor with plasma levels of leukocytes, neutrophils or C‐reactive protein between subjects with positive or negative aMMP‐8 immunotest. Conclusions: aMMP‐8 immunotest accuracy might be reduced, in relation to periodontitis, in haemato‐oncologic patients. [ABSTRACT FROM AUTHOR]

The effect of head and neck cancer (HNC) radiotherapy (RT) on biomarkers is not known but there is a lot of potential for gaining more precise cancer treatments and less side effects. This cohort study investigated the levels and molecular forms of the matrix metalloproteinase (MMP) -8 and -9, tissue inhibitor of metalloproteinase (TIMP)-1, myeloperoxidase (MPO) and interleukin (IL)-6 in mouth-rinse samples as well as the clinical periodontal status in HNC patients (n = 21) receiving RT. Complete periodontal examinations were performed pre-RT and one month after RT. Mouth-rinse samples (pre-RT, after six weeks of RT and one month after RT) were assayed using a point-of-care-kit (PerioSafe®/ORALyzer® (Dentognostics GmbH, Jena, Germany)) for active MMP-8 and ELISA analysis for total MMP-8 and -9, MPO, TIMP-1, and IL-6 levels. Molecular forms of MMP-9 were assessed by gelatinolytic zymography and MMP-8 by western immunoblot. Significant changes were observed between the three time points in the mean levels of active and total MMP-8, active MMP-9, and IL-6. Their levels increased during the RT and decreased after the RT period. The aMMP-8 levels stayed elevated even one month after RT compared to the pre-RT. Clinical attachment loss, probing depths, and bleeding on probing were increased between pre- and post-calculations in periodontal status. Elevated inflammatory biomarker levels together with clinical recordings strongly suggest that RT eventually increases the risk to the periodontal tissue destruction by inducing the active proteolytical MMP-cascade, and especially by prolonged activity of collagenolytic aMMP-8. Eventually, the aMMP-8 point-of-care mouth-rinse test could be an easy, early detection tool for estimating the risk for periodontal damage by the destructive MMP-cascade in HNC patients with RT treatment. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study is to examine correlations between different oral rinse matrix metalloproteinase (MMP)‐8 protein species in western blot (WB) analysis, quantitative MMP‐8 measurements, and patient‐related factors. Elevated activated MMP‐8 (aMMP‐8) associate with periodontitis and a diagnostic point‐of‐care technology has been developed based on aMMP‐8. In WB, different MMP‐8 protein species can be analyzed. Relative abundancy of fragmented 20–25 kDa forms in WB has been associated with and reflects MMP‐8 activation and related fragmentation and elevated quantitative aMMP‐8 measurements. Material and Methods: A random sample of 192 participants from a periodontal disease screening study was used for this study. Oral rinse samples for biomarker analyses were collected before clinical periodontal examinations. aMMP‐8 immunofluorometric (IFMA) and WB analysis (utilizing the same monoclonal antibody, 8708), polymorphonuclear leukocyte (PMN) elastase activity test and tissue inhibitor of metalloproteinases (TIMP)‐1 ELISA levels were performed from the oral rinse samples. Distinct MMP‐8 protein species were differentiated in the WB analysis. Principal component (PC) analysis was conducted to explore correlation patterns between the different species. Adjusted correlation analysis between the extracted PCs of WB and aMMP‐8 IFMA levels and multilevel regression analysis were conducted to explore if the other periodontal disease‐related biomarkers and clinical surrogate measures and patient‐related factors are co‐variating with the extracted components. Results: Distinct correlation patterns between the MMP‐8 protein species were observed. The first four PCs explained 89% of the whole variance in PC analysis. Statistically significant correlation (p < 0.05) were observed as follows: PC1 positively with 21 kDa (r =.69) and 25 kDa fragments (r =.55) and negatively with 150 kDa complexes (r = −.46). PC2 correlated with 45 (r =.70) and 55 kDa (r =.65) activated forms, PC3 with 70–80 kDa latent proforms (r =.63) and 90–100 kDa complexes (r =.67), and PC4 with 35 kDa fragments (r =.81). There were significant correlations between quantitative (IFMA) aMMP‐8 measurements and PC1 (p < 0.001), PC2 (<0.05) and PC3 (<0.05) but not with PC4. In multilevel regression models age, PMN elastase activity, TIMP‐1 levels, and a number of 4–5 mm periodontal pockets were associated with PC1, nonsmoking with PC2, age and PMN elastase activity with PC3, and age and smoking with PC4. Conclusions: Relative abundancy of fragmented 21–25 kDa protein species was correlated with the quantitative aMMP‐8 (IFMA) measurements, which is in line with previous results. Different patient‐related factors (smoking, age, proteolytic activity) may modify the formation of different MMP‐8 protein species in oral rinse samples and may cause variability in quantitative aMMP‐8 measurement. [ABSTRACT FROM AUTHOR]

This retrospective study addressed the role of oral potentially malignant disorders and the presence of intraepithelial Candida hyphae in the carcinogenesis of the oral tongue squamous cell carcinoma and its association with smoking, alcohol consumption, and oral inflammatory burden. The medical records of 183 subjects diagnosed with oral tongue squamous cell carcinoma at the Helsinki University Hospital were investigated. Preceding oral lichen planus, lichenoid reaction, and leukoplakia diagnosis were recorded. Further, the data on Candida hyphae in histological samples as an indicator of oral candidiasis, oral inflammatory burden, smoking, and alcohol consumption were recorded and analyzed. The histopathological diagnosis of oral lichen planus/lichenoid reaction (p < 0.001) and the presence of Candida hyphae (p = 0.005) were associated significantly with female gender. Oral lichen planus/lichenoid reaction patients were less often smokers than patients without these lesions. Candida hyphae were more often recorded in patients without alcohol use (p = 0.012). Oral lichen planus/lichenoid reaction and Candida hyphae in histological samples were associated with female gender and lower levels of typical risk factors, such as alcohol use and smoking, in oral tongue squamous cell carcinoma patients. Therefore, these patients should be well monitored despite a potential lack of the classical risk factors of oral carcinoma. [ABSTRACT FROM AUTHOR]

Background: The link between diabetes and periodontitis is bi-directional: high glucose levels increase the risk of periodontitis and elevated oral fluid aMMP-8 as well as diabetic development while untreated periodontitis worsens glycaemic control. Methods: Type-2 patients (N = 161) underwent an aMMP-8 Point-of-Care Test (POCT) at diabetes clinics. If the test was positive, the patient was sent to an oral health care clinic and oral health examination, health-promoting as well as necessary treatment procedures were carried out. Only 41 patients underwent full clinical evaluations. At the end of the treatment, an aMMP-8 POCT (B) was performed and if the test was positive, the treatment was continued and a new test (C) was performed, aiming for test negativity. The glycated haemoglobin (GHbA1c) test was performed approximately 6 months from the original appointment. Results: GHbA1c concentrations did not decrease during the follow-up. The concentrations of aMMP-8 assessed by POCT, and clinical parameters decreased. Changes in GHbA1c and aMMP-8 levels assessed by POCT during the treatment correlated positively with each other (p < 0.01). Conclusion: aMMP-8 POCT proved its reliability, and that its use is beneficial in the diabetes clinic, it enables identifying patients with periodontal findings reliably and guides them directly to an oral health clinic. [ABSTRACT FROM AUTHOR]

Introduction: The aim of the study was to compare the effects of a 30 µg/day versus 10 µg/day vitamin D supplementation, given during the two first years of life, on oral health at the age of six to 7 years. Methods: In 2013–2016, we conducted a randomized, double-blinded, clinical trial from age 2 weeks to 2 years of daily vitamin D3 supplementation (10 vs. 30 µg), including 975 healthy infants. For the present follow-up study at age 6–7 years, a sample of 123 children underwent oral examination by investigators blinded to the intervention group. Tooth enamel defect and caries findings, oral rinse active matrix metalloproteinase-8 levels, and tooth eruption were recorded. The intervention groups were compared with χ2 and Mann-Whitney U tests. Associations of the oral health outcomes were evaluated with correlation analysis and logistic regression. Results: Of the children (median age 7.4 years, 51% boys), 56% belonged to the 30 µg intervention group. Developmental defect of enamel (DDE) was found in 39% of the children in the 10 µg intervention group and in 53% of the 30 µg group (p = 0.104). In total, 94% of children were vitamin D sufficient (25[OH]D ≥50 nmol/L) and 88% had caries-free teeth. No associations were found between vitamin D intervention group in infancy and oral health or the presence of DDE. Conclusion: Daily supplementation with 10 µg vitamin D3 in the Northern Hemisphere seems adequate in healthy children younger than 2 years in ensuring good oral health at early school age. [ABSTRACT FROM AUTHOR]

Objective: To analyse the correspondence between aMMP-8 PoC test results and the clinical endpoints of non-surgical periodontal treatment in stage III/IV periodontitis. Background: The diagnostic success of the active-matrix metalloproteinase-8 (aMMP-8) point-of- care (PoC) test has been demonstrated in various studies, but the evidence of its accuracy following periodontal treatment is limited. Materials and methods: Altogether 42 stage III/IV grade C periodontitis patients were included in this prospective diagnostic study. Clinical periodontal indices were recorded, aMMP-8 PoC test was applied and mouthrinse was collected before and at 6, 12 and 24 weeks after non-surgical periodontal treatment. Quantitative aMMP-8 levels were determined with immunofluorometric assay (IFMA) for the verification of the PoC test results. The accuracy of the aMMP-8 PoC test was assessed using previously established clinical endpoints as references. Results: Sensitivity and specificity of aMMP-8 PoC test to indicate clinical endpoints were ranged as follows: Sensitivity 71.4% at baseline, 39.3%–42.4% at week 6, 28.6%–32.4% at week 12 and 35.3%–42.9% at week 24; specificity 64.3%–80% at week 6, 40%–57.1% at week 12 and 56%–64.3% at week 24. Conclusions: The accuracy of aMMP-8 PoC test in identifying clinical endpoints after non-surgical periodontal treatment is reduced in relation to baseline. Individual healing patterns of each diseased pocket eventually limit the accuracy of the dichotomous aMMP-8 oral rinse test during the post-treatment period. [ABSTRACT FROM AUTHOR]

Background: Previous studies have revealed the potential diagnostic utility of aMMP-8, an active form of MMP-8, in periodontal and peri-implant diseases. While non-invasive point-of-care (PoC) chairside aMMP-8 tests have shown promise in this regard, there is a dearth of literature on the evaluation of treatment response using these tests. The present study aimed to investigate treatment-related changes in aMMP-8 levels in individuals with Stage III/IV—Grade C periodontitis compared to a healthy control group, using a quantitative chairside PoC aMMP-8 test, and to determine its correlation with clinical parameters. Methods: The study included 27 adult patients (13 smoker, 14 non-smoker) with stage III/IV-grade C periodontitis and 25 healthy adult subjects. Clinical periodontal measurements, real-time PoC aMMP-8, IFMA aMMP-8, and Western immunoblot analyses were performed before and 1 month after anti-infective scaling and root planing periodontal treatment. Time 0 measurements were taken from the healthy control group to test the consistency of the diagnostic test. Results: Both PoC aMMP-8 and IFMA aMMP-8 tests showed a statistically significant decrease in aMMP-8 levels and improvement in periodontal clinical parameters following treatment (p < 0.05). The PoC aMMP-8 test had high diagnostic sensitivity (85.2%) and specificity (100.0%) for periodontitis and was not affected by smoking (p > 0.05). Treatment also reduced MMP-8 immunoreactivity and activation as demonstrated by Western immunoblot analysis. Conclusion: The PoC aMMP-8 test shows promise as a useful tool for the real-time diagnosis and monitoring of periodontal therapy. [ABSTRACT FROM AUTHOR]

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Objectives: We aimed to study the effects of fermented lingonberry juice (FLJ) as a mouthwash on the levels of active matrix metalloproteinase‐8 (aMMP‐8) in peri‐implant sulcular fluid (PISF), bleeding on probing (BOP), and visible plaque index (VPI). We hypothesized that FLJ rinsing could reduce inflammation (aMMP‐8 and BOP) and microbial load (VPI) in the oral cavity, especially around dental implants. Materials and Methods: A clinical pilot study was performed using FLJ as a mouthwash. The inclusion criteria were at least one dental implant in the anterior or posterior areas with a screw‐retained crown. Ten participants used 10 ml of mouthwash twice a day for 15 days, and 10 participants served as the control group. Point‐of‐care tests (POCTs) were used to measure aMMP‐8 levels in the PISF, and BOP and VPI were recorded at the beginning of the trial and after 15 and 30 days. Results: The FLJ mouthwash had a reductive effect on aMMP‐8, VPI, and BOP in the mouthwash group; however, there was no significant difference compared to the control group. The difference in VPI and BOP levels between the groups diminished after the lingonberry regimen ended. The decrease in aMMP‐8 levels appeared to continue even after discontinuation of the mouthwash regimen. Conclusion: The reduction in the amount of plaque, aMMP‐8, and BOP by FLJ was promising and continuous considering the relatively short study period and sample size. FLJ is a natural and safe supplement for oral and dental implant home care. Further studies are required to verify these promising results. [ABSTRACT FROM AUTHOR]

A single-site, randomized clinical trial was designed to determine the efficacy of regular home use of Lumoral® dual-light antibacterial aPDT in periodontitis patients. For the study, 200 patients were randomized to receive non-surgical periodontal treatment (NSPT), including standardized hygiene instructions and electric toothbrush, scaling and root planing, or NSPT with adjunctive Lumoral® treatment. A complete clinical intraoral examination was conducted in the beginning, at three months, and at six months. This report presents the three-month results of the first 59 consecutive randomized subjects. At three months, bleeding on probing (BOP) was lower in the NSPT + Lumoral®-group than in the NSPT group (p = 0.045), and more patients in the NSPT + Lumoral®-group had their BOP below 10% (54% vs. 22%, respectively, p = 0.008). In addition, patients in the NSPT + Lumoral®-group improved their oral hygiene by visible-plaque-index (p = 0.0003), while the NSPT group showed no statistical improvement compared to the baseline. Both groups significantly reduced the number of deep periodontal pockets, but more patients with a reduction in their deep pocket number were found in the NSPT + Lumoral® group (92% vs. 63%, p = 0.02). Patients whose number of deep pockets was reduced by 50% or more were also more frequent in the NSPT + Lumoral®-group (71% vs. 33%, p = 0.01). Patients with initially less than ten deep pockets had fewer deep pockets at the three-month follow-up in the Lumoral® group (p = 0.01). In conclusion, adjunctive use of Lumoral® in NSPT results in improved treatment outcomes at three months post-therapy. [ABSTRACT FROM AUTHOR]

In colorectal cancer (CRC), systemic inflammation is associated with poor prognosis, but the underlying mechanisms are not fully characterized. Tumor necrosis may contribute to systemic inflammation by inducing interleukin (IL)-6 signaling, and proinflammatory cytokines such as IL-6 and IL-8, and matrix metalloproteinase (MMP)-8 also are linked to adverse CRC outcomes. Because Toll-like receptors (TLRs) are important mediators of inflammatory responses, we investigated the roles of TLR2 and TLR4 in CRC-associated systemic inflammatory responses, especially tumor necrosis. In 118 patients with CRC, extensive tumor necrosis was associated with low TLR4 expression in tumor cells. Tumor cell TLR4 expression was inversely correlated with serum IL-6 and MMP-8 levels, blood total leukocyte and neutrophil counts, and serum C-reactive protein levels. Tumor cell TLR2 expression was not significantly associated with necrosis or systemic inflammation, but low expression in normal mucosa was linked to high serum MMP-8 and IL-8. These findings indicate that tumor necrosis is associated with low TLR4 expression in cancer cells and that low TLR4 expression correlates with a strong systemic inflammatory response. The low TLR2 expression in normal mucosa and its association with systemic inflammation suggest that the normal mucosa may reflect or contribute to the systemic inflammatory response. [ABSTRACT FROM AUTHOR]

Objectives: Periodontitis is a multifactorial biofilm‐induced inflammatory disease; however, clinical and radiographic information reflects events that have already occurred. aMMP‐8 lateral‐flow chairside or point‐of‐care‐test (POC‐test) results have also come to complement the overall status of the patient's current situation. The current study aimed to clarify the usefulness of aMMP‐8 chairside‐test (aMMP‐8 POCT) results to alert the initial or early periodontitis in adolescents, a potential periodontitis risk group with cut off 20 ng/ml in Stage I periodontitis, according to the current periodontitis classification system. Material and Methods: A total of 117 adolescents were aMMP‐8 POC tested for aMMP‐8 levels and examined for the full mouth and were interviewed for questions concerning health behavior. Results: Of all 117 participants, N = 38 (32.5%) was aMMP‐8 POCT positive, and N = 34 (29.1%) had at least one 4 mm periodontal deepened pocket; however, only N = 16 (13.7%) had both characteristics. The subclinical stage (N = 47) could not be classified either as gingivitis or Stage I. Of the participants, who did not have any deepened periodontal pockets, 18 tested negative. Conclusions: Stage I is preceded by antecedent stages that should be tackled by oral healthcare prevention and personalized treatment modalities by professionals. Elevated (>20 ng/ml), positive aMMP‐8 POCT results can be regarded as initial alarmer such as emerging risk. This should be utilized in the preventive personalized interventions by oral health professionals. [ABSTRACT FROM AUTHOR]

Objectives. In the preterm infant, lung injury can lead to irreversible tissue destruction and abnormal lung development. We examined whether pulmonary trypsin, a potent matrix-degrading serine proteinase and proteinase-cascade activator, is associated with the development of bronchopulmonary dysplasia (BPD) in preterm infants. Methods. Samples of tracheal aspirate fluid were collected from 32 intubated preterm infants during their first 2 postnatal weeks. The presence and molecular forms of trypsin in tracheal aspirate fluid samples were analyzed by zymography and Western blotting. The concentrations of trypsinogen-1 and -2 and tumor-associated trypsin inhibitor were measured by immunofluorometry. For examining the expression of trypsin-2 in lung tissue, immunohistochemistry was performed on autopsy specimens of fetuses, of preterm infants who died from respiratory distress syndrome or BPD, and of term infants without lung injury. Results. In infants who subsequently developed BPD (n = 18), we detected significantly higher concentrations of trypsinogen-2 during postnatal days 5 to 10 compared with those who survived without it. There was no difference in trypsinogen-1 concentrations. Tumor-associated trypsin inhibitor concentrations were significantly lower in infants who needed mechanical ventilation for >1 week. Immunohistochemistry demonstrated that trypsin-2 was predominantly expressed in bronchial and bronchiolar epithelium. In 2 preterm infants who died from prolonged respiratory distress syndrome, trypsin-2 was also expressed in vascular endothelium. Conclusions. The levels of trypsinogen-2 are higher during postnatal days 5 to 10 in infants who subsequently develop BPD. The results suggest that high levels of pulmonary trypsin-2 may be associated with the development of BPD. This raises the possibility that therapy with exogenous proteinase inhibitors might prevent the development of BPD in preterm infants with respiratory distress. Pediatrics 2003;112:570-577; trypsin, preterm infants, respiratory distress syndrome, bronchopulmonary dysplasia., Trypsin is a serine proteinase secreted as a zymogen (trypsinogen) in pancreatic fluid and activated by enterokinase in the intestine, where it plays an important role as a food-digestive enzyme. [...]

Objective: The aim of this study was to determine the diagnostic utility of an MMP‐8 biosensor assay in differentiating periodontal health from gingivitis and periodontitis and compare it with an established time‐resolved immunofluorescence assay (IFMA) and enzyme‐linked immunosorbent assay (ELISA). Background: Currently available antibody‐based assays display a wide variability in their ability to accurately measure matrix metalloproteinase‐8 (MMP‐8) levels in saliva. Methods: Salivary MMP‐8 levels were analyzed in 189 systemically healthy participants using an antibody‐based biosensor prototype that operates using a surface acoustic wave technology and compared with IFMA and ELISA antibody assays. Participants were categorized into 3 groups: periodontal health (59), gingivitis (63), and periodontitis (67). A sub‐population of participants (n = 20) with periodontitis received periodontal treatment and were monitored for 6 months. Results: All the assays demonstrated significantly higher salivary MMP‐8 concentrations in participants with periodontitis versus gingivitis, periodontitis versus health, and gingivitis versus health (all p <.05). The biosensor data demonstrated significant correlations with IFMA (r =.354, p <.001) and ELISA (r =.681, p <.001). Significant reductions in salivary MMP‐8 concentrations were detected by the biosensor (p =.030) and IFMA (p =.002) in participants with periodontitis 6 months after non‐surgical periodontal treatment. IFMA had the best sensitivity (89.2%) for detecting periodontitis and gingivitis versus health and 96.6% for detecting periodontitis versus health and gingivitis. The biosensor had an AUC value of 0.81 and diagnostic accuracy of 74.2% for differentiating periodontitis and gingivitis from health; an AUC value of 0.86 and diagnostic accuracy of 82.8% for periodontitis versus health and gingivitis. Conclusions: The biosensor, IFMA, and ELISA assays differentiated between periodontal health, gingivitis, and periodontitis based on salivary MMP‐8 levels. Only the biosensor and, particularly, IFMA identified an effect of periodontal treatment in the participants with periodontitis. Our findings support the potential utility of salivary oral fluid aMMP‐8‐based point‐of‐care technology in the future of periodontal diagnostics. [ABSTRACT FROM AUTHOR]