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,... more
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.
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ABSTRACT Inflammatory cytokines such as tumor necrosis factor-alpha are involved in the pathogenesis of periodontal diseases. A high between-subject variation in the level of tumor necrosis factor-alpha mRNA has been verified, which may... more
ABSTRACT Inflammatory cytokines such as tumor necrosis factor-alpha are involved in the pathogenesis of periodontal diseases. A high between-subject variation in the level of tumor necrosis factor-alpha mRNA has been verified, which may be a result of genetic polymorphisms and/or the presence of periodontopathogens such as Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola (called the red complex) and Aggregatibacter actinomycetemcomitans. In this study, we investigated the effect of the tumor necrosis factor-alpha (TNFA) -308G/A gene polymorphism and of periodontopathogens on the tumor necrosis factor-alpha levels in the periodontal tissues of nonsmoking patients with chronic periodontitis (n = 127) and in control subjects (n = 177). The TNFA -308G/A single nucleotide polymorphism was investigated using polymerase chain reaction-restriction fragment length polymorphism analysis, whereas the tumor necrosis factor-alpha levels and the periodontopathogen load were determined using real-time polymerase chain reaction. No statistically significant differences were found in the frequency of the TNFA -308 single nucleotide polymorphism in control and chronic periodontitis groups, in spite of the higher frequency of the A allele in the chronic periodontitis group. The concomitant analyses of genotypes and periodontopathogens demonstrated that TNFA -308 GA/AA genotypes and the red-complex periodontopathogens were independently associated with increased levels of tumor necrosis factor-alpha in periodontal tissues, and no additive effect was seen when both factors were present. P. gingivalis, T. forsythia and T. denticola counts were positively correlated with the level of tumor necrosis factor-alpha. TNFA -308 genotypes were not associated with the periodontopathogen detection odds or with the bacterial load. Our results demonstrate that the TNFA -308 A allele and red-complex periodontopathogens are independently associated with increased levels of tumor necrosis factor-alpha in diseased tissues of nonsmoking chronic periodontitis patients and consequently are potentially involved in determining the disease outcome.
Research Interests: Genetics, Dentistry, Biology, Medicine, Humans, and 15 moreFemale, Male, Bacteria, Polymerase Chain Reaction, Middle Aged, Genotype, Adult, Periodontitis, Chronic Periodontitis, Adenine, Periodontal, PORPHYROMONAS GINGIVALIS, Aggregatibacter actinomycetemcomitans, Periodontal Pocket, and Gene frequency
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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... more
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.
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The pathogenesis of obesity-related vascular disorders has not been fully elucidated. The fundamental role of inflammation in aging process is now widely recognized, particularly for atherosclerotic disease which begins before birth. The... more
The pathogenesis of obesity-related vascular disorders has not been fully elucidated. The fundamental role of inflammation in aging process is now widely recognized, particularly for atherosclerotic disease which begins before birth. The number of obese individuals worldwide has reached two billion, leading to an explosion of obesity-related vascular disorders associated with increased morbidity and mortality. Obesity, as a chronic low grade inflammatory process, is important risk factor for metabolic and cardiovascular disease. Despite a well-known genetic component, this risk appears to originate from several abnormalities in adipose tissue function associated with a chronic inflammatory state. In particular, obesity as the most common nutritional disorder in industrialized countries, is closely related to impaired endothelial function, a well-known marker of preatherosclerotic disease. These conditions disrupt vascular homeostasis by causing an imbalance between the nitric oxide ...
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The pathogenesis of obesity-related vascular disorders has not been fully elucidated. The fundamental role of inflammation in aging process is now widely recognized, particularly for atherosclerotic disease which begins before birth. The... more
The pathogenesis of obesity-related vascular disorders has not been fully elucidated. The fundamental role of inflammation in aging process is now widely recognized, particularly for atherosclerotic disease which begins before birth. The number of obese individuals worldwide has reached two billion, leading to an explosion of obesity-related vascular disorders associated with increased morbidity and mortality. Obesity, as a chronic low grade inflammatory process, is important risk factor for metabolic and cardiovascular disease. Despite a well-known genetic component, this risk appears to originate from several abnormalities in adipose tissue function associated with a chronic inflammatory state. In particular, obesity as the most common nutritional disorder in industrialized countries, is closely related to impaired endothelial function, a well-known marker of preatherosclerotic disease. These conditions disrupt vascular homeostasis by causing an imbalance between the nitric oxide ...
Research Interests: Inflammation and Medicine
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AIM To investigate the possible association between TNFα (-308 G/A) and IL-1β (-511 C/T) single nucleotide polymorphisms (SNPs) and GSTT and GSTM deletion polymorphisms and risk of apical periodontitis (AP) development, and determine the... more
AIM To investigate the possible association between TNFα (-308 G/A) and IL-1β (-511 C/T) single nucleotide polymorphisms (SNPs) and GSTT and GSTM deletion polymorphisms and risk of apical periodontitis (AP) development, and determine the association of different genotypes with the presence of herpesviral infection in AP. METHODOLOGY The study included 120 periapical lesions and 200 control samples. Gene polymorphism analysis was performed using either polymerase chain reaction (PCR) or PCR/ restriction fragment length polymorphism (RFLP). Relative gene expression of TNF-α and IL-1β was analysed using reverse transcriptase - real-time PCR. The presence of Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) was assessed by nested PCR. Chi square and Fisher exact tests, and logistic regression analyses were done for polymorphisms, while Mann Whitney U-test was performed for the expression analysis. The expected frequency of variants was analysed by the Hardy-Weinberg equilibrium test. RESULTS TNF-α (-308 G/A) SNP increased AP susceptibility for heterozygous (Odds Ratio (OR) = 1.72, 95% Confidence Interval (CI) = 1.06-2.80, P = 0.027) and homozygous (OR = 8.55, 95% CI = 1.77-41.36, P < 0.001) carriers of the variant A allele. On the other hand, IL-1β (-511 C/T) polymorphism exerted a protective effect both in heterozygotes (OR = 0.540, 95% CI = 0.332-0.880, P = 0.013) and homozygotes (OR = 0.114, 95% CI = 0.026-0.501, P < 0.001). In addition, GSTM1 and GSTT1 null genotypes separately, as well as concomitantly were associated with an increased risk for AP development (P < 0.001). The null GSTT1 genotype increased approximately twice the risk of Epstein-Barr infection (EBV) in AP (OR= 2.17, 95% CI=1-4.71, P=0.048), while TNF-α SNP decreased it, both in heterozygotes (OR=0.20, 95% CI= 0.08-0.48, P<0.001) and AA homozygotes (OR=0.07, 95% CI=0.01-0.37, P=0.001). CONCLUSIONS GSTM and GSTT deletion polymorphisms, as well as TNFα (-308 G/A) SNP, are associated with increased risk, whereas IL-1β (-511 C/T) polymorphism decreases the risk of AP development. GSTT and TNFα polymorphisms also appear to modulate the risk of EBV infection in Serbian patients with apical periodontitis.
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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... more
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.
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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... more
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. The literature search covered MEDLINE, Science Citation Index Expanded, and Scopus. A qualitative critical appraisal of the included articles was performed. 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 resorpt...
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Mesenchymal stem cells (MSCs) were isolated from human periodontal ligament (hPDL-MSCs) and characterized by their morphology, clonogenic efficiency, proliferation and differentiation capabilities. hPDL-MSCs, derived from normal impacted... more
Mesenchymal stem cells (MSCs) were isolated from human periodontal ligament (hPDL-MSCs) and characterized by their morphology, clonogenic efficiency, proliferation and differentiation capabilities. hPDL-MSCs, derived from normal impacted third molars, possessed all of the properties of MSC, including clonogenic ability, high proliferation rate and multi-lineage (osteogenic, chondrogenic, adipogenic, myogenic) differentiation potential. Moreover, hPDL-MSCs expressed a typical MSC epitope profile, being positive for mesenchymal cell markers (CD44H, CD90, CD105, CD73, CD29, Stro-1, fibronectin, vimentin, ?-SMA), and negative for hematopoietic stem cell markers (CD34, CD11b, CD45, Glycophorin-CD235a). Additionally, hPDL-MSCs, as primitive and highly multipotent cells, showed high expression of embryonic markers (Nanog, Sox2, SSEA4). The data obtained provided yet further proof that cells with mesenchymal properties can be obtained from periodontal ligament tissue. Although these cells s...
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We review the potential of plasma medical applications, the connections to nanotechnologies and the results obtained by our group. A special issue in plasma medicine is the development of the plasma sources that would achieve... more
We review the potential of plasma medical applications, the connections to nanotechnologies and the results obtained by our group. A special issue in plasma medicine is the development of the plasma sources that would achieve non-equilibrium at atmospheric pressure in atmospheric gas mixture with no or only marginal heating of the gas, and with desired properties and mechanisms that may be controlled. Our studies have shown that control of radicals or chemically active products of the discharge such as ROS (reactive oxygen species) and/or NO may be used to control the growth of the seeds. At the same time specially designed plasma needle and other sources were shown to be efficient to sterilize not only colonies of bacteria but also planctonic samples (microorganisms protected by water) or bio films. Finally we have shown that plasma may induce differentiation of stem cells. Non-equilibrium plasmas may be used in detection of different specific markers in medicine. For example proto...
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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... more
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. 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% O, He + 1.5% O), 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% O 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. NTAP significantly reduced contact angles of reference liquids and increased dentin SFE com...
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Constantly growing field of biomedical applications is a new frontier that drives the development of plasma sources. The choice of the plasma system used for treatment is usually guided by the type of samples that are treated and effect... more
Constantly growing field of biomedical applications is a new frontier that drives the development of plasma sources. The choice of the plasma system used for treatment is usually guided by the type of samples that are treated and effect these plasmas are intended to have on the samples. Some of the samples cannot undergo vacuum and due to this fact non-thermal atmospheric pressure plasmas lately have drawn considerable attention with their enormous potential for technological applications in surface modifications and biomedical applications. The necessity to use plasma for in-vivo treatments/procedures has led to several requirements for plasma sources to meet. Because of its mild plasma, low gas temperature and geometry, the plasma needle is especially convenient for medical applications. We have studied effect of the plasma needle on different living cells, from plants through bacteria such as Escherichia coli and Staphylococcus aureus to the human peripheral blood mesenchymal ste...
To investigate possible applications of plasma needle in biomedicine we performed experiments studying effects of plasma needle on different species of bacteria in a planctonic form and staphylococcus aureus biofilms. In this study... more
To investigate possible applications of plasma needle in biomedicine we performed experiments studying effects of plasma needle on different species of bacteria in a planctonic form and staphylococcus aureus biofilms. In this study standard strains of four species were used: Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922). Pseudomonas auriginosa (ATCC 27853) and Enterococcus faecalis (ATCC 29212) in order to study deactivation of harmful bacteria. Possible plasma needle application in treatments of light bacterial infections, such as in-vivo sterilization of skin and dental cavities was our main motivation. Most importantly the study is made to see the effects when the living cells are in liquid medium which normally acts as a protection against many agents that may be released by plasmas. It was found that a goods effect may be expected for a wide range of initial cell densities and operating conditions giving destruction of several orders of magnitude even under ...
There are many types of plasmas that can be generated under ambient pressure and temperature conditions, the need for precise and localized treatments qualifies plasma needle to be a good match [1]. Because of its mild plasma, low gas... more
There are many types of plasmas that can be generated under ambient pressure and temperature conditions, the need for precise and localized treatments qualifies plasma needle to be a good match [1]. Because of its mild plasma, low gas temperature and geometry, the plasma needle is especially convenient for medical applications. This device can be used for non-contact disinfection of dental cavities and wounds, minimum-destructive precise treatment, as well as the removal of damaged tissue. Our measurements were performed on a standard size plasma needle that we originally used for the treatment of plant cells [2]. In this paper we will present results of plasma needle treatments on the human peripheral blood-derived multipotent mesenchymal stem cells (hPB-MSC) (fibroblast cells). We have treated cells in two conditions, i.e. with and without liquid environment (suspension). Results from the MTT viability and Crystal Violet adhesion tests performed with the hPB-MSC will be presented....
In this paper we will present results for plasma sterilization of planktonic samples of two reference strains of bacteria, Pseudomonas aeruginosa ATCC 27853 and Enterococcus faecalis ATCC 29212. We have used a plasma needle as a source of... more
In this paper we will present results for plasma sterilization of planktonic samples of two reference strains of bacteria, Pseudomonas aeruginosa ATCC 27853 and Enterococcus faecalis ATCC 29212. We have used a plasma needle as a source of non-equilibrium atmospheric plasma in all treatments. This device is already well characterized by OES, derivative probes and mass spectrometry. It was shown that power delivered to the plasma is bellow 2 W and that it produces the main radical oxygen and nitrogen species believed to be responsible for the sterilization process. Here we will only present results obtained by electron paramagnetic resonance which was used to detect the OH, H and NO species. Treatment time and power delivered to the plasma were found to have the strongest influence on sterilization. In all cases we have observed a reduction of several orders of magnitude in the concentration of bacteria and for the longest treatment time complete eradication. A more efficient steriliz...
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The interleukin (IL)-17 producing T-helper cells have been linked to pathogenesis of autoimmunity and mostly investigated in rheumatoid arthritis (RA). In this study we tested the IL-17 levels, as well as the levels of nitric oxide (NO)... more
The interleukin (IL)-17 producing T-helper cells have been linked to pathogenesis of autoimmunity and mostly investigated in rheumatoid arthritis (RA). In this study we tested the IL-17 levels, as well as the levels of nitric oxide (NO) as possible IL-17-induced product, in patients with primary Sjögren's syndrome (pSS), an intricate and complex chronic autoimmune disorder of exocrine glands. Serum IL-17 levels and nitrite concentrations determined in patients with pSS (n=30) were compared with the values obtained in patients with RA (n=10) and healthy controls (n=15). The values obtained for IL-17 in pSS patients were also associated with the patients' clinical characteristics, particularly the rheumatoid factor (RF) and total antinuclear antibodies (tANA) levels. Serum concentrations of IL-17 were significantly (P<0.01) higher in patients with pSS (12.9 ± 28.0 pg/ml) as compared to those obtained in healthy individuals (0.2 ± 0.6 pg/ml), but not as high as the values ob...
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The interleukin (IL)-17 producing T-helper cells have been linked to pathogenesis of autoimmunity and mostly investigated in rheumatoid arthritis (RA). In this study we tested the IL-17 levels, as well as the levels of nitric oxide (NO)... more
The interleukin (IL)-17 producing T-helper cells have been linked to pathogenesis of autoimmunity and mostly investigated in rheumatoid arthritis (RA). In this study we tested the IL-17 levels, as well as the levels of nitric oxide (NO) as possible IL-17-induced product, in patients with primary Sjögren's syndrome (pSS), an intricate and complex chronic autoimmune disorder of exocrine glands. Serum IL-17 levels and nitrite concentrations determined in patients with pSS (n=30) were compared with the values obtained in patients with RA (n=10) and healthy controls (n=15). The values obtained for IL-17 in pSS patients were also associated with the patients' clinical characteristics, particularly the rheumatoid factor (RF) and total antinuclear antibodies (tANA) levels. Serum concentrations of IL-17 were significantly (P<0.01) higher in patients with pSS (12.9 ± 28.0 pg/ml) as compared to those obtained in healthy individuals (0.2 ± 0.6 pg/ml), but not as high as the values ob...