Human gingival epithelial cells stimulate proliferation, migration, and tube formation of lymphatic endothelial cells in vitro

Objective The aim of this study was to investigate the response of gingival epithelial cells to microbial and inflammatory signals. Background The gingival epithelial barrier provides the first line of defense and supports tissue homeostasis by maintaining the cross-talk between gingival epithelium, oral microbiota, and immune cells. Lymphatic vessels are essential to sustaining this homeostasis. The gingival epithelial cells have been shown to produce prolymphangiogenic factors during physiologic conditions, but their role in response to microbial and inflammatory signals is unknown. Methods Immortalized human gingival epithelial cells (HGEC) and human dermal lymphatic microvascular endothelial cells (LEC) were cultured. HGEC were exposed to Porphyromonas gingivalis derived-LPS, human IL-1 beta/IL-1F2 protein, or recombinant human IL-6/IL-6R. Levels of vascular growth factors (VEGF-A, VEGF-C, and VEGF-D) in cell supernatants were determined by ELISA. LEC were grown to confluence, and a scratch was induced in the monolayer. Uncovered area was measured up to 48 h after exposure to conditioned medium (CM) from HGEC. Tube formation assays were performed with LEC cocultured with labelled HGEC or exposed to CM. Results VEGF-A, VEGF-C, and low levels of VEGF-D were constitutively expressed by HGEC. The expression of VEGF-C and VEGF-D, but not VEGF-A, was upregulated in response to proinflammatory mediators. VEGF-C was upregulated in response to P. gingivalis LPS, but not to Escherichia coli LPS. A scratch migration assay showed that LEC migration was significantly increased by CM from HGEC. Both the CM and coculture with HGEC induced significant tube formation of LEC. Conclusions HGEC can regulate production of lymphangiogenic/angiogenic factors during inflammatory insults and can stimulate proliferation, migration, and tube formation of LEC in vitro in a paracrine manner.publishedVersio

Volume of blood suctioned during vacuum-assisted breast biopsy predicts later hematoma formation

<p>Abstract</p> <p>Background</p> <p>To evaluate whether the volume of blood suctioned during vacuum-assisted breast biopsy (VABB) is associated with hematoma formation and progression, patient's age and histology of the lesion.</p> <p>Findings</p> <p>177 women underwent VABB according to standardized protocol. The volume of blood suctioned and hematoma formation were noted at the end of the procedure, as did the subsequent development and progression of hematoma. First- and second-order logistic regression was performed, where appropriate. Cases with hematoma presented with greater volume of blood suctioned (63.8 ± 44.7 cc vs. 17.2 ± 32.9 cc; p < 0.001, Mann-Whitney-Wilcoxon test for independent samples, MWW); the likelihood of hematoma formation was increasing till a volume equal to 82.6 cc, at which the second-order approach predicts a maximum. The volume of blood suctioned was positively associated with the duration of the procedure (Spearman's rho = 0.417, p < 0.001); accordingly, hematoma formation was also positively associated with the latter (p = 0.004, MWW). The volume of blood suctioned was not associated with patients' age, menopausal status and histopathological diagnosis.</p> <p>Conclusion</p> <p>The likelihood of hematoma is increasing along with increasing amount of blood suctioned, reaching a plateau approximately at 80 cc of blood lost.</p

Breast ductal endoscopy: how many procedures qualify?

This is an open access article distributed under the terms of the Creative Commons Attribution Licens

Oral health-related quality of life in 4-16-year-olds with and without juvenile idiopathic arthritis

Background: Few studies have investigated oral health-related quality of life (OHRQoL) in young individuals with juvenile idiopathic arthritis (JIA). Aims were to investigate whether OHRQoL differs between children and adolescents with JIA compared to controls without JIA, while adjusting for socio-demographic-, behavioral- and oral health-related covariates. Furthermore, to explore whether socio-behavioral and oral health-related covariates of OHRQoL vary according to group affiliation and finally, specifically for individuals with JIA, to investigate whether disease-specific features associate with OHRQoL. We hypothesized that participants with JIA have poorer OHRQoL compared to participants without JIA. Methods: In this comparative cross-sectional study participants with JIA (n = 224) were matched to controls without JIA (n = 224). OHRQoL was assessed according to Early Childhood Oral Health Impact Scale (ECOHIS) (4–11-years-olds) and the child version of Oral Impacts on Daily Performances (Child-OIDP) (12–16-years-olds). JIA-specific characteristics were assessed by pediatric rheumatologists and socio-demographic, behavioral and self-reported oral health information collected by questionnaires. Index teeth were examined for caries by calibrated dentists. Multiple variable analyses were performed using logistic regression, reporting odds ratio (OR) and 95% confidence interval (CI). Two-way interactions were tested between group affiliation and the socio-behavioral- and oral health-related variables on the respective outcome variables. Results: In total, 96 participants with JIA and 98 controls were evaluated according to ECOHIS, corresponding numbers for Child-OIDP was 125 and 124. Group affiliation was not associated with impaired ECOHIS or Child-OIDP in adjusted analyses (OR = 1.95, 95% CI 0.94–4.04 and OR = 0.99, 95% CI 0.46–2.17, respectively). Female adolescents with JIA were more likely than males to report oral impacts according to Child-OIDP. Continued activity or flare was found to adversely affect Child-OIDP, also self-reported outcome measures in JIA associated with Child-OIDP. Conclusions: This study did not provide consistent evidence to confirm the hypothesis that children and adolescents with JIA are more likely to have impaired OHRQoL compared to their peers without JIA. However, female adolescents with JIA were more likely than males to report impacts on OHRQoL. Furthermore, within the JIA group, adolescents with continued disease activity, flare or reporting pain, physical disability, had higher risk than their counterparts of impaired OHRQoL.publishedVersio

Vitamin D, oral health, and disease characteristics in juvenile idiopathic arthritis: a multicenter cross-sectional study

Background: Vitamin D defciency has been associated with autoimmune diseases and oral health. Knowledge about the association between vitamin D status and oral conditions in JIA is limited. We aimed to investigate vitamin D status in a cohort of Norwegian children and adolescents with JIA and possible associations between serum vitamin D levels, clinical indicators of oral health, and JIA disease characteristics. Methods: This multi-center, cross-sectional study, included individuals with JIA aged 4–16 years from three geographically spread regions in Norway. Demographic data, age at disease onset, disease duration, JIA category, disease status, medication, and vitamin D intake were registered. One blood sample per individual was analyzed for 25(OH) vitamin D, and the level of insufciency was defned asResults: Among the 223 participants with JIA, 97.3% were Caucasians, 59.2% were girls, and median age was 12.6 years. Median disease duration was 4.6 years, and 44.4% had oligoarticular JIA. Mean serum vitamin D level was 61.4 nmol/L and 29.6% had insufcient levels. Vitamin D levels did not difer between sexes, but between regions, isoBMI categories, age groups, and seasons for blood sampling. Insufcient vitamin D levels were associated with dentin caries (adjusted OR 2.89, 95% CI 1.43–5.86) and gingival bleeding (adjusted OR 2.36, 95% CI 1.10–5.01). No associations were found with active JIA disease or more severe disease characteristics. Conclusion: In our study, nearly 30% had vitamin D insufciency, with a particularly high prevalence among adolescents. Vitamin D insufciency was associated with dentin caries and gingival bleeding, but not with JIA disease activity. These results point to the need for a multidisciplinary approach in the follow-up of children with JIA, including an increased focus on vitamin D status and oral health

The prognostic role of galectin-3 and endothelial function in patients with heart failure

Background: Heart failure (HF) is nowadays classified as HF with reduced ejection fraction (HFrEF), HF with mildly reduced EF (HFmrEF), and HF with preserved EF (HFpEF). Endothelial dysfunction (assessed by flow-mediated dilatation [FMD]), increased arterial stiffness (assessed by carotid-femoral pulse-wave velocity [PWV]), and galectin-3, a biomarker of myocardial fibrosis, have been linked to major adverse cardiovascular events (MACE) in patients with ischemic HF. Methods: In this study we prospectively enrolled 340 patients with stable ischemic HF. We assessed the brachial artery FMD, carotid-femoral PWV, and galectin-3 levels, and patients were followed up for MACE according to EF group. Results: Interestingly, the FMD values exhibited a stepwise improvement according to left ventricular ejection fraction (LVEF) (HFrEF: 4.74 ± 2.35% vs. HFmrEF: 4.97 ± 2.81% vs. HFpEF: 5.94 ± 3.46%, p = 0.01), which remained significant after the evaluation of possible confounders including age, sex, cardiovascular risk factors, and number of significantly stenosed epicardial coronary arteries (b coefficient: 0.990, 95% confidence interval: 0.166–1.814, p = 0.019). Single-vessel coronary artery disease (CAD) was more frequent in the group of HFpEF (HFrEF: 56% vs. HFmrEF: 64% vs. HFpEF: 73%, p = 0.049). PWV did not display any association with LVEF. Patients who presented MACE exhibited worse FMD values (4.51 ± 2.35% vs. 5.32 ± 2.67%, p = 0.02), and the highest tertile of galectin-3 was linked to more MACEs (36% vs. 5.9%, p = 0.01). Conclusions: Flow-mediated dilatation displayed a linear improvement with LVEF in patients with ischemic HF. Deteriorated values are associated with MACE. Higher levels of galectin-3 might be used for risk stratification of patients with ischemic HF

Endogenous viral elements in shrew genomes provide insights into Pestivirus ancient history

As viral genomic imprints in host genomes, endogenous viral elements (EVEs) shed light on the deep evolutionary history of viruses, ancestral host ranges, and ancient viral-host interactions. In addition, they may provide crucial information for calibrating viral evolutionary timescales. In this study, we conducted a comprehensive in silico screening of a large dataset of available mammalian genomes for EVEs deriving from members of the viral family Flaviviridae, an important group of viruses including well-known human pathogens, such as Zika, dengue, or hepatitis C viruses. We identified two novel pestivirus-like EVEs in the reference genome of the Indochinese shrew (Crocidura indochinensis). Homologs of these novel EVEs were subsequently detected in vivo by molecular detection and sequencing in 27 shrew species, including 26 species representing a wide distribution within the Crocidurinae subfamily and one in the Soricinae subfamily on different continents. Based on this wide distribution, we estimate that the integration event occurred before the last common ancestor of the subfamily, about 10.8 million years ago, attesting to an ancient origin of pestiviruses and Flaviviridae in general. Moreover, we provide the first description of Flaviviridae-derived EVEs in mammals even though the family encompasses numerous mammal-infecting members. This also suggests that shrews were past and perhaps also current natural reservoirs of pestiviruses. Taken together, our results expand the current known Pestivirus host range and provide novel insight into the ancient evolutionary history of pestiviruses and the Flaviviridae family in general

Decreasing NF-κB Expression Enhances Odontoblastic Differentiation and Collagen Expression in Dental Pulp Stem Cells Exposed to Inflammatory Cytokines

Inflammatory response in the dental pulp can alter the collagen matrix formation by dental pulp stem cells and lead to a delay or poor healing of the pulp. This inflammatory response is mediated by cytokines, including interleukin-1β and tumor necrosis factor-α. In this study, it is hypothesized that suppressing the actions of these inflammatory cytokines by knocking down the activity of transcription factor Nuclear Factor–κB will lead to dental pulp stem cell differentiation into odontoblasts and the production of collagen. Here, the role of Nuclear Factor–κB signaling and its reduction was examined during odontogenic behavior in the presence of these cytokines. The results showed a significant increase in Nuclear Factor–κB gene expression and p65 protein expression by interleukin-1β and tumor necrosis factor-α. Nuclear Factor–κB activation in the presence of these cytokines decreased significantly in a dose-dependent manner by a Nuclear Factor–κB inhibitor (MG132) and p65 siRNA. Down-regulation of Nuclear Factor–κB activity also enhanced the gene expression of the odontoblastic markers (dentin sialophosphoprotein, Nestin, and alkaline phosphatase) and displayed an odontoblastic cell morphology indicating the promotion of odontogenic differentiation of dental pulp stem cells. Finally, dental pulp stem cells exposed to reduced Nuclear Factor–κB activity resulted in a significant increase in collagen (I)-α1 expression in the presence of these cytokines. In conclusion, a decrease in Nuclear Factor-κB in dental pulp stem cells in the presence of inflammatory cytokines enhanced odontoblastic differentiation and collagen matrix formation.The open access fee for this work was funded through the Texas A&M University Open Access to Knowledge (OAK) Fund