Exploring the Link between Hydrodynamic Size and Immunoglobulins of Circulating Immune Complexes in Rheumatoid Arthritis Patients.

The function of immune complexes in rheumatoid arthritis (RA) is related to their composition and size. Using dynamic light scattering (DLS), we investigated the link between the RA circulating immune complex (CIC) particles' size and the CIC immunoglobulin level. In this study, 30 RA patients and 30 healthy individuals were included. IgA, IgG, and IgM were found in all analyzed CICs, but more IgA and IgG were found in RA than in control CICs. In both control and RA CICs, DLS detected 50 particles that differed in size and clustered around two size groups: with a 7.5-164 nm radius and with a 342-1718 nm radius. An increased level of IgA in RA CICs, compared to control ones, was associated with more than 50% of CIC particles. In RA, compared to the control, a higher number of CICs with 28.2 nm, 531 nm, 712 nm, and 1718 nm particles and a lower number of CICs with 78.8 nm particles were detected. This particle distribution pattern did not reflect the changes in the CIC immunoglobulin level. Thus, RA elevated CIC IgA was linked with all these particles (except the 1718 nm particle), the IgM increase was linked with 43.8 nm and 712 nm particles, and the IgG increase was linked with the 712 nm particle only. This study provides the very first data on the association between CIC particles' size, CIC immunoglobulin level, and RA. It opens the possibility that the size of CICs determined by DLS can be used as a criterion in RA diagnosis or monitoring after a large-scale study confirmation.

Modulating stemness of mesenchymal stem cells from exfoliated deciduous and permanent teeth by IL-17 and bFGF.

Mesenchymal stem cells (MSCs) have been identified within dental pulp tissues of exfoliated deciduous (SHEDs) and permanent (DPSCs) teeth. Although differences in their proliferative and differentiation properties were revealed, variability in SHEDs and DPSCs responsiveness to growth factors and cytokines have not been studied before. Here, we investigated the influence of interleukin-17 (IL-17) and basic fibroblast growth factor (bFGF) on stemness features of SHEDs and DPSCs by analyzing their proliferation, clonogenicity, cell cycle progression, pluripotency markers expression and differentiation after 7-day treatment. Results indicated that IL-17 and bFGF differently affected SHEDs and DPSCs proliferation and clonogenicity, since bFGF increased proliferative and clonogenic potential of both cell types, while IL-17 similarly affected SHEDs, exerting no effects on adult counterparts DPSCs. In addition, both factors stimulated NANOG, OCT4, and SOX2 pluripotency markers expression in SHEDs and DPSCs showing diverse intracellular expression patterns dependent on MSCs type. As for the differentiation capacity, both factors displayed comparable effects on SHEDs and DPSCs, including stimulatory effect of IL-17 on early osteogenesis in contrast to the strong inhibitory effect showed for bFGF, while having no impact on SHEDs and DPSCs chondrogenesis. Moreover, bFGF combined with IL-17 reduced CD90 and stimulated CD73 expression on both types of MSCs, whereas each factor induced IL-6 expression indicating its' role in IL-17/bFGF-modulated properties of SHEDs and DPSCs. All these data demonstrated that dental pulp MSCs from primary and permanent teeth exert intrinsic features, providing novel evidence on how IL-17 and bFGF affect stem cell properties important for regeneration of dental pulp at different ages.

Tumor Necrosis Factor Alpha -308 G/A Single-Nucleotide Polymorphism and Apical Periodontitis: An Updated Systematic Review and Meta-analysis.

INTRODUCTION: This study aimed to perform a more precise estimation of the association between tumor necrosis factor alpha (TNF-α) -308 G/A single-nucleotide polymorphism (SNP) and the risk of development of apical periodontitis (AP) and its phenotypes based on all available published studies. METHODS: The study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and is registered in PROSPERO (CRD42020176190). The literature search was conducted via Clarivate Analytics Web of Science, Scopus, PubMed, Cochrane Central Register of Controlled Trials, and China National Knowledge Infrastructure databases from inception to December 2020 with no language restrictions. Two reviewers were involved independently in the study selection, data extraction, and appraising the studies that were included. The quality of the included studies was evaluated using the Strengthening the Reporting of Genetic Association and the Grading of Recommendations Assessment, Development and Evaluation system. The frequencies of the genotypes and alleles of the TNF-α (G>A 308, rs1800629) gene with 95% odds ratio were used. RESULTS: Four studies met the inclusion criteria with moderate risk of bias. This study revealed no significant association between TNF-α -308 G/A SNP and AP and the risk of AP development. Moreover, there was no significant association between genotype or allele frequency distribution and clinical manifestations (acute vs chronic) of AP. The certainty of evidence per the Grading of Recommendations Assessment, Development and Evaluation system was very low. CONCLUSIONS: Because of very low certainty of evidence, whether there is an association between TNF-α -308 G/A SNP and AP warrants further well-designed multicentric studies to adjudicate a better understanding of the role of genetic factors in the etiopathogenesis of AP.

Prevalence of Apical Periodontitis and Conventional Nonsurgical Root Canal Treatment in General Adult Population: An Updated Systematic Review and Meta-analysis of Cross-sectional Studies Published between 2012 and 2020.

INTRODUCTION: This study aimed to summarize data on apical periodontitis (AP) and nonsurgical root canal treatment (NSRCT) prevalence and risk factors related to age, gender, and quality of restorative and endodontic treatment in the general population from cross-sectional studies published between 2012 and 2020. METHODS: An electronic search was performed in the following databases: Web of Science, Scopus, and PubMed. The conducted literature search covered studies published between 2012 and 2020, without restrictions on language. The STROBE and NOS tools were used for quality assessment of the included studies. RESULTS: Sixteen articles were included in the review. In total, 200,041 teeth were examined. On average, 6.3% of teeth had AP, and 7.4% had NSRCT. Forty-one percent of RCT teeth had AP, and 3.5% of untreated teeth had AP. Female patients were less prone to AP in endodontically treated teeth only, compared with male patients (P < .001). Variable stratification of age subgroups among included studies prevented us from conducting a meta-analysis. An increase in AP frequency was found in teeth with inadequate restorative and endodontic treatment (P < .001 and P < .001, respectively). Because of high heterogeneity, these results should be taken with caution. CONCLUSIONS: There is an increased AP prevalence in the adult general population compared with data from 2012 (6.3% versus 5.4%) in both endodontically treated (41.3% versus 35.9%) and untreated teeth (3.5% versus 2.1%). In addition, AP developed less frequently in female patients with endodontically treated teeth and in teeth with inadequate compared with adequate restorative and endodontic treatment.

Infection as a predictor of mortality in decompensated liver cirrhosis: exploring the relationship to severity of liver failure.

BACKGROUND: Infections are common in patients with liver cirrhosis and increase mortality. We explored the relationship between infection and liver dysfunction in their effects on mortality. METHODS: Single-center data on decompensated liver cirrhosis patients hospitalized between March 2014 and December 2017 (index period) were reviewed until death, liver transplantation or 31 December 2018. Infections were classified as community-acquired infection (CAi) or hospital/healthcare associated infection (HCAi). Child-Pugh, model for the end-stage liver disease (MELD) and chronic liver failure-organ failure (CLiF-OF) scores indicated liver (dys)function. RESULTS: We enrolled 155 patients (85% alcoholic liver disease), 65 without infection at first hospitalization, 48 with CAi and 42 with HCAi. Multidrug resistant agents were confirmed in 2/48 (4.2%) CAi and 10/42 (23.8%) HCAi patients. At first hospitalization, infection was independently associated with worse liver dysfunction and vice versa, and with higher 30-day mortality [odds ratio (OR) = 2.73, 95% confidence interval (CI) 1.07-6.94]. The association was reduced with adjustment for MELD/CLiF-OF scores, but mediation analysis detected an indirect (via liver dysfunction) association. Twenty-eight patients were repeatedly hospitalized, 11 with new HCAi. HCAi was independently associated with twice higher risk of medium-term mortality and added an additional risk to any level of liver dysfunction, considering all or patients who survived the first 30 days. In those repeatedly hospitalized, HCAi appeared independently associated with a higher probability of infection and higher MELD scores at subsequent hospitalizations. CONCLUSION: Infection (particularly HCAi) adds mortality risk to any level of liver dysfunction in decompensated liver cirrhosis patients. Mechanisms of long(er)-term effects (in acute episode survivors) seemingly include enhanced deterioration of liver function.

Notch - a possible mediator between Epstein-Barr virus infection and bone resorption in apical periodontitis.

Objectives: This study aimed to investigate whether Epstein-Barr virus (EBV) positive periapical lesions exhibited higher mRNA levels of Notch signalling molecules (Notch2 and Jagged1), bone resorption regulators (receptor activator of nuclear factor kappa-ß ligand (RANKL) and osteoprotegerin (OPG)), and proinflammatory cytokines (tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß) and IL-6) compared to EBV negative lesions. Additionally, the potential correlation between investigated molecules in periapical lesions was analyzed.Materials and methods: Sixty-four apical periodontitis lesions were obtained subsequent to standard apicoectomy procedure. The presence of EBV was determined using nested PCR. Based on the presence of EBV all periapical lesions were divided into two groups, 29 EBV positive and 35 EBV negative lesions. A reverse transcriptase real-time PCR was used to determine mRNA levels of Notch2, Jagged1, RANKL, OPG, TNF-α, IL-1ß and IL-6.Results: Significantly higher mRNA levels of Notch2, Jagged1, RANKL and IL-1ß were observed in EBV positive compared to EBV negative lesions. Significant positive correlation was present between Notch2 and Jagged1, Jagged1 and RANKL, and IL-ß and TNF-α in EBV positive periapical lesions.Conclusions: Notch signalling pathway may be involved in alveolar bone resorption in apical periodontitis lesions infected by EBV.

Notch signaling pathway mediates alveolar bone resorption in apical periodontitis.

Apical periodontitis represents a chronic inflammatory process within periapical tissues, mostly caused by etiological agents of endodontic origin. Progressive bone resorption in the periapical region represents the hallmark of apical periodontitis and occurs as the consequence of interplay between polymicrobial infections and host response. The Notch signaling pathway is an evolutionary conserved cell-signaling system that plays an important role in a variety of cell functions including proliferation, differentiation and apoptosis. In recent years its involvement in bone homeostasis has attracted a significant consideration. We hypothesized that Notch signaling pathway, which has a complex interplay with proinflammatory cytokines and bone resorption regulators, contributes to alveolar bone resorption via increased Notch receptors on immune cell surface and stimulates Notch receptor intracellular domain (NICD) translocation into the nucleus. The potential benefit of medications aimed to down-regulate these pathways in apical periodontitis treatment remains to be assessed.

Effects of non-thermal atmospheric plasma treatment on dentin wetting and surface free energy for application of universal adhesives.

OBJECTIVES: The study aims to evaluate the effects of non-thermal atmospheric plasma (NTAP) treatments on dentin wetting and surface free energy (SFE) and compare the effects of NTAP treatment, etch-and-rinse, and self-etch protocols for application of universal adhesives. MATERIALS AND METHODS: Mid-coronal dentin of intact third molars was used to measure contact angles of distilled water, ethylene-glycol, and diiodomethane and calculate SFE following different NTAP preset treatments (feeding gas consisting of pure He, He + 1% O2, He + 1.5% O2), power input (1 or 3 W), and tip-to-surface distance (2, 4, or 8 mm). Contact angles of reference liquids and SFE of dentin following He + 1.5% O2 at 3-W and 4-mm treatment was compared to phosphoric acid etching. Contact angles of Single Bond Universal (SBU; 3M ESPE) and Clearfil Universal Bond (CUB; Kuraray Noritake) were measured following NTAP, etch-and-rinse, and self-etch protocols. RESULTS: NTAP significantly reduced contact angles of reference liquids and increased dentin SFE compared to untreated dentin (p < 0.05). O2 intensified the effect of He NTAP (p < 0.05). NTAP and phosphoric acid increased dentin polarity and Lewis base surface characteristics. Phosphoric acid increased contact angles of adhesives compared to the self-etch protocol (p < 0.05). NTAP resulted in lower adhesive contact angles than phosphoric acid, the difference being statistically significant for CUB (p < 0.05). Compared to the self-etch protocol, NTAP slightly reduced CUB contact angle but not that of SBU (p > 0.05). CONCLUSIONS: He NTAP with and without O2 increased dentin wetting and SFE, surpassing the effect of phosphoric acid and lowering adhesive contact angles. NTAP produced no apparent micro-morphological changes on dentin surface comparable to acid etching. CLINICAL SIGNIFICANCE: NTAP treatment of dentin prior to adhesive application increases dentin wetting and surface free energy facilitating better adhesive distribution on dentin surface compared to phosphoric acid etching and similar to the "self-etch" application protocol.

Notch Signaling Pathway in Apical Periodontitis: Correlation with Bone Resorption Regulators and Proinflammatory Cytokines.

INTRODUCTION: The exact mechanisms of periapical bone resorption have not been fully elucidated. This study aimed to analyze the expression of Notch signaling molecules (Notch2, Jagged1, and Hey1) and proinflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin [IL]-1ß, and IL-6) in human apical periodontitis lesions with different receptor activator of nuclear factor kappa B ligand (RANKL)/osteoprotegerin (OPG) ratios and determine their potential correlation. METHODS: The study group consisted of 50 periapical lesions collected in conjunction with apicoectomy. The relative gene expression of the investigated molecules (Notch2, Jagged1, Hey1, RANKL, OPG, TNF-α, IL-1ß, and IL-6) in all tissue samples was analyzed using reverse transcriptase real-time polymerase chain reaction. The Student t test, Mann-Whitney U test, and Spearman correlation were used for statistical analysis. RESULTS: Based on the RANKL/OPG ratio, periapical lesions were either RANKL predominant (RANKL > OPG, n = 33) or OPG predominant (RANKL < OPG, n = 17). Symptomatic lesions occurred more frequently in RANKL-predominant compared with OPG-predominant lesions (24 vs 7, P = .029). Notch2, Jagged1, Hey1, and TNF-α were significantly overexpressed in lesions with predominant RANKL compared with lesions with predominant OPG (P = .001, P = .001, P = .027, and P = .016, respectively). Significant correlations were observed between the investigated genes in periapical lesions. CONCLUSIONS: Notch signaling appeared to be activated in periapical inflammation. An increase in Notch2, Jagged1, Hey1, and TNF-α expression in RANKL-predominant periapical lesions corroborates their joined involvement in extensive periapical bone resorption.

The Role of Varicella Zoster Virus in the Development of Periapical Pathoses and Root Resorption: A Systematic Review.

INTRODUCTION: Varicella zoster virus (VZV) and subsequent herpes zoster (HZ) infection have been proposed as a causative agent of periapical pathoses and root resorption. This review aimed to identify, synthesize, and present a critical analysis of the available data on the association among VZV, subsequent HZ infection, and the development of periapical pathoses and root resorption and to analyze the level of evidence of available studies. METHODS: The literature search covered MEDLINE, Science Citation Index Expanded, and Scopus. A qualitative critical appraisal of the included articles was performed. RESULTS: The electronic database search yielded 66 hits from PubMed, 73 hits from Web of Science, and 107 from Scopus. Seven case reports and 3 cross-sectional studies were included in the final review. When summarized, in 7 patients with a history of a previous HZ attack and with no other apparent cause, 23 teeth were diagnosed with apical periodontitis, 8 teeth with internal and 1 tooth with external root resorption. The cross-sectional studies investigated the presence of VZV DNA in samples of acute apical abscess. The VZV DNA was found only in 2 of 65 samples. CONCLUSIONS: All studies included in this systematic review had a low level of evidence (4 and 5). Still, the potential role of VZV in the etiopathogenesis of periapical pathoses and root resorption cannot be ruled out. Future investigations should be directed toward the analysis of VZV pathologic effects on pulp blood vessels, which might cause local ischemia and tissue necrosis.

Epstein-Barr virus infection induces bone resorption in apical periodontitis via increased production of reactive oxygen species.

Chronic inflammatory processes in periapical tissues caused by etiological agents of endodontic origin lead to apical periodontitis. Apart from bacteria, two herpesviruses, Epstein-Barr virus (EBV) and Human cytomegalovirus (HCMV) are recognized as putative pathogens in apical periodontitis. Although previous reports suggest the involvement of EBV in the pathogenesis of apical periodontitis, its exact role in periapical bone resorption has not yet been fully elucidated. We hypothesize that EBV infection in apical periodontitis is capable of inducing periapical bone resorption via stimulation of reactive oxygen species (ROS) overproduction. Increased levels of ROS induce expression of receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL). RANKL binding to receptor activator of nuclear factor κB (RANK) present on the surface of preosteoclasts induces their maturation and activation which consequently leads to bone resorption. The potential benefit of antiviral and antioxidant-based therapies in periapical bone resorption treatment remains to be assessed.