SEM analysis of the endodontic cavity wall after removal of restorative materials used as temporary restoration.

AIM: The aim of the present in vitro study was to analyze the endodontic cavity walls for presence of remnants of conventional glass ionomer cement and flowable light cure composite used as temporary restorative materials of endodontically treated teeth. The dentine surface of the access cavity was observed with scanning electron microscopy after the final removal of the temporary restoration using high-speed turbine and diamond bur or ultrasonic device and diamond tip.

Alzheimer's disease: the hypotheses, known and unknown connections between UV-radiation, mtDNA haplotypes and life span - a review.

Alzheimer's disease (AD) is the most common neurodegenerative disease with controversial etiology. One theory claims that AD is due to brain aging affecting mainly the functions of mitochondria, therefore, the factors leading to mitochondrial ageing should lead to the development of Alzheimer's disease. Another theory is that different mitochondrial DNA haplogroups can be predisposition for the onset of the condition. Here we focused on the possible connection between AD and UV radiation using the data on the monthly UV index in Europe, its correlation with mortality rate due to AD and mitochondrial DNA haplogroups distribution. If a link between the two theories is proved, it will mean that UV radiation is a risk factor not only for skin cancer but also for a large group of neurodegenerative diseases amongst which is the Alzheimer's disease.

Amination of Graphene Oxide Leads to Increased Cytotoxicity in Hepatocellular Carcinoma Cells.

Clinically, there is an urgent need to identify new therapeutic strategies for selectively treating cancer cells. One of the directions in this research is the development of biocompatible therapeutics that selectively target cancer cells. Here, we show that novel aminated graphene oxide (haGO-NH2) nanoparticles demonstrate increased toxicity towards human hepatocellular cancer cells compared to pristine graphene oxide(GO). The applied novel strategy for amination leads to a decrease in the size of haGO-NH2 and their zeta potential, thus, assuring easier penetration through the cell membrane. After characterization of the biological activities of pristine and aminated GO, we have demonstrated strong cytotoxicity of haGO-NH2 toward hepatic cancer cells - HepG2 cell line, in a dose-dependent manner. We have presented evidence that the cytotoxic effects of haGO-NH2 on hepatic cancer cells were due to cell membrane damage, mitochondrial dysfunction and increased reactive oxygen species (ROS) production. Intrinsically, our current study provides new rationale for exploiting aminated graphene oxide as an anticancer therapeutic.

Aminated Graphene Oxide as a Potential New Therapy for Colorectal Cancer.

Nanotechnology-based drug delivery systems for cancer therapy are the topic of interest for many researchers and scientists. Graphene oxide (GO) and its derivates are among the most extensively studied delivery systems of this type. The increased surface area, elevated loading capacity, and aptitude for surface functionalization together with the ability to induce reactive oxygen species make GO a promising tool for the development of novel anticancer therapies. Moreover, GO nanoparticles not only function as effective drug carriers but also have the potential to exert their own inhibitory effects on tumour cells. Recent results show that the functionalization of GO with different functional groups, namely, with amine groups, leads to increased reactivity of the nanoparticles. The last steers different hypotheses for the mechanisms through which this functionalization of GO could potentially lead to improved anticancer capacity. In this research, we have evaluated the potential of amine-functionalized graphene oxide nanoparticles (GO-NH2) as new molecules for colorectal cancer therapy. For the purpose, we have assessed the impact of aminated graphene oxide (GO) sheets on the viability of colon cancer cells, their potential to generate ROS, and their potential to influence cellular proliferation and survival. In order to elucidate their mechanism of action on the cellular systems, we have probed their genotoxic and cytostatic properties and compared them to pristine GO. Our results revealed that both GO samples (pristine and aminated) were composed of few-layer sheets with different particle sizes, zeta potential, and surface characteristics. Furthermore, we have detected increased cyto- and genotoxicity of the aminated GO nanoparticles following 24-hour exposure on Colon 26 cells. The last leads us to conclude that exposure of cancer cells to GO, namely, aminated GO, can significantly contribute to cancer cell killing by enhancing the cytotoxicity effect exerted through the induction of ROS, subsequent DNA damage, and apoptosis.

Impact of a High-fat Diet on the Development of Chronic Inflammation in Heart of Wistar rats.

INTRODUCTION: Obesity is linked to the development of low-grade, chronic inflammation. Obesity-related inflammation appears to be a different type of inflammation, mainly due to excessive food intake and unusual homeostasis. It can be evaluated by measuring the concentration of pro- and anti-inflammatory marker molecules ­ C-reactive protein (CRP), serum amyloid-A (SAA) and interleukin-4. AIM: The aim of the present study is to evaluate the rate of the inflammatory process in heart, provoked by the consumption of a high-fat diet. MATERIALS AND METHODS: Sixty 8-week-old male Wistar rats were used in this experiment. The laboratory animals were fed orally with two different types of rodent food for 14 or 18 weeks ­ a high-fat diet (experimental groups) and standard rodent food (control groups). They all were kept under standard housing conditions. The levels of the pro- and anti-inflammatory markers in tissue homogenates from heart were analyzed using ELISA. Their expression in tissue samples was detected immunohistochemically by the biotin-streptavidin-peroxidase method. The total protein concentration was determined by the Lawry method. RESULTS: CRP levels showed no significant differences when the control group was compared with the groups fed with a high-fat diet (p>0.05). The SAA levels detected were also insignificantly changed. Only the IL-4 tissue levels showed tendency to increase (p<0.05) in the high-fat diet group. CONCLUSIONS: Our experiment indicates that there is a specific reaction of the heart to a high-fat diet. It also refers to the existence of adaptive mechanisms allowing the heart to counteract the development of dietary induced inflammation.

Linker histones and chromatin remodelling complexes maintain genome stability and control cellular ageing.

Linker histones are major players in chromatin organization and per se are essential players in genome homeostasis. As the fifth class of histone proteins the linker histones not only interact with DNA and core histones but also with other chromatin proteins. These interactions prove to be essential for the higher levels of chromatin organization like chromatin loops, transcription factories and chromosome territories. Our recent results have proved that Saccharomyces cerevisiae linker histone - Hho1p, physically interacts with the actin-related protein 4 (Arp4) and that the abrogation of this interaction through the deletion of the gene for the linker histone in arp4 mutant cells leads to global changes in chromatin compaction. Here, we show that the healthy interaction between the yeast linker histone and Arp4p is critical for maintaining genome stability and for controlling cellular sensitivity to different types of stress. The abolished interaction between the linker histone and Arp4p leads the mutant yeast cells to premature ageing phenotypes. Cells die young and are more sensitive to stress. These results unambiguously prove the role of linker histones and chromatin remodelling in ageing by their cooperation in pertaining higher-order chromatin compaction and thus maintaining genome stability.

Effects of Low Level Laser Therapy on Erosive-atrophic Oral Lichen Planus.

BACKGROUND: The erosive-atrophic form of oral lichen planus (OLP) is associated with severe pain and burning sensation and is often unresponsive to treatment. Topical corticosteroids are considered as a medication of first choice but they can produce adverse effects. Therefore, new therapeutic approaches are required. AIM: The aim of this study was to investigate the effectiveness of biomodulation with diode laser in patients presenting with long-standing erosive-atrophic OLP. MATERIALS AND METHODS: Twelve patients, clinically and histologically diagnosed with OLP, participated in this study. The level of pain and the clinical scores of total 59 lesions were recorded before treatment using visual analog scale and Thongprasom sign scoring system respectively. All patients received low level laser therapy (LLLT) with diode laser (810 nm) with parameters (0.5 W, 30 s, 1.2 J/cm2) three times weekly for a month. The response rate was assessed according to the decrease in pain and sign scores. Treatment efficacy index was calculated. RESULTS: There was a significant reduction in pain after LLLT (p<0.0001). Improvement in clinical signs was achieved in 59.3% of the lesions. At the end of the treatment 5.1% of the lesions exhibited score 5; 6.8% - score 4, 11.9% of the lesions were scored 3 and 8.5% and 30.5% showed score 2 and score 1, respectively. Complete resolution was revealed in 37.3% of the lesions. All patients experienced some degree of improvement. Most of the cases showed moderate recovery. CONCLUSION: The present results indicate that LLLT is an effective and harmless modality for management of erosive-atrophic OLP.

Circulating levels of interleukin-17A, tumor necrosis factor-alpha, interleukin-18, interleukin-10, and cognitive performance of patients with relapsing-remitting multiple sclerosis.

Multiple sclerosis (MS) is associated with cytokine imbalance and high rate (40-70%) of cognitive impairment. The objective of this study is to investigate the relationship between serum concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-17A, IL-18, IL-10, and cognitive performance in patients with relapsing-remitting MS (RRMS). Methods The study comprised 159 patients with RRMS (mean age 40.08 ± 8.48 years) in remission phase and 86 age-, gender-, and education-matched healthy controls. Paced Auditory Serial Addition Test (PASAT), Symbol Digit Modalities test (SDMT), and Isaacs test were used for assessment of working memory, attention, visuo-perceptual abilities, information processing speed, and executive functions. Serum cytokine concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Results Patients had significantly increased serum concentrations of TNF-alpha and IL-17A and decreased levels of IL-10 compared to the controls (p < 0.05). Negative correlation was found between serum TNF-alpha and SDMT score in patients with disease evolution longer than 10 years (rxy = -0.258 p = 0.033); PASAT and SDMT scores were in negative correlation with concentration of IL-17A (rxy = -0.229 p = 0.004; rxy = -0.166 p = 0.041). Cognitive impairment was established in 46.5% (n = 74) of the patients. Cognitively impaired patients had significantly higher serum IL-17A than cognitively preserved individuals (p = 0.007). Multiple linear regression analysis revealed IL-17A as a significant predictor of cognitive performance in RRMS patients. Conclusion The results from this study suggest that pro-inflammatory cytokines IL-17A and TNF-alpha simultaneously with decreased IL-10 are involved in cognitive deterioration in RRMS.

Oral Lichen Planus - Known and Unknown: a Review.

Lichen planus is a chronic mucocutaneous inflammatory disease aff ecting 1-2% of the general population with maximum prevalence of the disease in women above the age of 40. Its aetiology remains unclear and the pathogenesis is still the object of much speculation. It is considered to be an autoimmune disorder mediated mainly by the T-lymphocytes. The present paper presents the most well-known external agents (viruses in particular), internal agents like stress, and the heat shock protein thought to be trigger factors and describes the action of diff erent cells and proteins associated with the development of that disease. Diagnosis is based on clinical and histopathologic evidence; direct and indirect immunofluorescence techniques can also be of use. Despite the wide variety of therapeutic modalities, treatment outcomes are often insufficient. Currently, topical corticosteroids are widely accepted as a standard therapy, but also retinoids, calcineurin inhibitors and other immunosuppressants can be administered. Because of the aspect relevant to these drugs, priority is given to alternative harmless methods such as LLLT and PDLT. There is an ongoing controversy in the literature about the possible premalignant character of oral lichen planus, however, periodic followup is recommended.

In vivo investigation of antihyperalgesic and antinociceptive effects of peat formulations.

The aim of this study is to evaluate the antihyperalgesic and antinociceptive effects of two formulations containing peat water extracts using a model of carrageenan-induced hyperalgesia, combined with a test with a mechanical stimulus, and a hot plate test. Rats were divided into seven groups (n = 6) and received local treatment with two peat formulations and two diclofenac formulations dissolved in carbopol gel and Wolff® basis creme, respectively. Carbopol gel, Wolff® basis creme and 0.9 % NaCl without tested substances were used as controls. Both peat formulations exerted an unambiguous antihyperalgesic effect 60 minutes after the treatment. In the hot plate test, the rats treated with the Wolff® basis creme peat formulation showed a tendency to prolonged latency on the first hour. The results could be explained by partial activation of peripheral α2-adrenoceptors and the possible COX-2 suppressive activity.

Effects of propolis and CAPE on proliferation and apoptosis of McCoy-Plovdiv cell line.

UNLABELLED: The mechanisms of action of propolis can be studied in detail by comparing the effects of propolis and the effects of its constituent components. AIM: To clarify and compare the effects of Bulgarian propolis and caffeic acid phenethyl ester (CAPE, a chemically synthesized component of propolis)--by using a set of cellular, molecular-biological and immunological techniques. MATERIAL AND METHODS: The McCoy-Plovdiv cell line was treated with propolis and CAPE in increasing concentrations (0.01, 0.1, 1.0, 10 mg/L, and 2.5, 4, 8, 16 mg/L, respectively). The expression of the proliferating cell nuclear antigen (PCNA) and the tumour-suppressor protein p53 was studied immunocytochemically. Apoptosis was measured using a highly sensitive microgel electrophoresis technique (comet assay). RESULTS: The results of the study showed corresponding changes in the expression of the examined proliferative antigens. PCNA was detected in all examined concentrations of the tested substances the expression being dose-dependent. Molecule localization changed from the nucleus to the cytoplasm. Treatment with CAPE brought about gradual attenuation of PCNA expression. High propolis concentrations induced increased synthesis of p53. No p53 expression was found when cells were treated with CAPE. The studied substances in their highest concentrations (10 mg/L propolis and 16 mg/L CAPE) had a cytotoxic effect. The comet assay showed DNA degradation kinetics characteristic for apoptosis. CONCLUSIONS: The present study demonstrates that high concentrations of propolis and CAPE cause apoptosis-induced cell death in McCoy-Plovdiv cells.