Novel Aortic Valve Replacement Technique for Reducing Complete Heart Block.

Background: Aortic valve replacement (AVR) may complicate conduction abnormalities and require permanent pacemaker (PPM) implantation. New techniques that lessen this challenge may lead to the development of new approaches. Our objective was to evaluate the contemporary incidence of early postoperative PPM implantation in patients undergoing isolated AVR and root disease with the standard AVR surgical technique compared with the novel suture AVR technique. Methods: The clinical data of 354 patients (250 male, 104 female) who underwent surgery for isolated AVR and root disease in different referral cardiology departments in Tabriz, Iran, over 4 years were analyzed. Patients with preoperative significant conduction abnormalities were excluded from the study. The patients were evaluated for in-hospital mortality, postoperative PPM implantation, and their stay in the ICU after surgery. Results: The mean age of the patients was 52.46±16.13 years. Totally, 183 patients (51.7%) were operated on with the new suture AVR technique. In-hospital mortality was lower in this group than in the group that underwent the "classic" surgical technique (2.5% vs 3.7%). PPM implantation was required in 3 patients (0.8%) after the novel suture AVR technique, whereas it was needed in 12 patients (3.4%) in the other group (P=0.024). The mortality rate was 9 patients (2.5%) in group 1 and 13 patients (3.7%) in group 2, which was not statistically significant (P=0.296). According to the logistic regression, the survival rate in the group operated on with the classical surgical method was 0.27 times higher than that in the patients operated on with the new method. Conclusion: Permanent complete AV block is a critical complication after AVR surgery. A lower PPM requirement and higher survival in patients operated on with the new method was the main finding of this study. New techniques with lower PPM requirements may be suitable for cardiac surgery.

Alantolactone and ZnO nanoparticles induce apoptosis activity of cisplatin in an ovarian cancer cell line (SKOV3).

Background and purpose: Ovarian cancer is one of the leading causes of cancer mortality in women. Despite the increase in cases of this cancer, the current therapeutic strategy is not effective. This study aimed to investigate the effect of cisplatin (Cis) with alantolactone (ALT) and ZnO nanoparticles (ZnONPs) in inducing apoptosis in SKOV3 ovarian cancer cells line. Experimental approach: To evaluate the viability of SKOV3 cells and determine the IC50 of Cis, ALT, and ZnONPs, MTT assay was used. Real-time PCR and western blotting were used to evaluate the expression levels of genes (XIAP, cyclin D1, Bcl-2, Bax, and MDM2) and proteins (XIAP, cyclin D1, Bcl-2, Bax), respectively. Also, cellular ROS levels were assessed by fluorimetry. Findings / Results: Our results showed that ALT and ZnONPs significantly increased the response to Cis in SKOV3 cells compared to the control and this response is remarkably increased in the triple combination (ALT-Cis-ZnONPs). The expression of XIAP, cyclin D1, and Bcl-2 genes and proteins in the groups treated with ALT, Cis, and ZnONPs as a single agent, double and triple combination were significantly reduced compared to the control, while Bax was generally shown an increase. Also, the level of intracellular ROS is higher in the treatment groups than in the control group and the highest increase was observed in the triple combination. Conclusion and implications: Taken together, our data demonstrated the potential therapeutic approach of using ALT and ZnONPs that may enhance the apoptotic effects of Cis on the SKOV3 cells.

Effects of anti-TNF biologic drugs on uveitis severity in Behçet patients: systematic review and Meta-analysis.

AIM: To investigate effects of anti-TNF biologic drugs on uveitis severity (comparing visual acuity logMAR levels) in Behçet patients. METHODS: Three databases PubMed, Scopus, and the Web of Science were searched for qualified papers focusing on the anti-TNF-α factors treatment in Behçet's disease (BD)-associated uveitis. Studies that were designed pre and post anti-TNF drug treatment, were selected. After determining the search strategy for this study, the relevant data were extracted. RESULTS: The initial search was performed in the target databases and a total of about 1458 articles were found. Fifteen articles were selected for systematic review and only 12 of them had inclusion criteria for Meta-analysis (with visual acuity data). The mean dose of prednisolone before and after biological treatments was reported in 5 studies (28.56 and 7.56 mg/kg, respectively). Also, the preliminary results indicate a significant reduction in visual acuity logMAR levels (MD=-1.5 IU/L, 95%CI: -2.1, -0.01). CONCLUSION: Biological drugs significantly reduce the dose of prednisolone and affect visual acuity values.

Efficacy of mental-incisive nerve block in root canal treatment of mandibular first molars with asymptomatic irreversible pulpitis: a randomized controlled trial.

The aim of this study was to evaluate the effect of mental-incisive nerve block (MINB) along with finger pressure following inferior alveolar nerve block (IANB) on anesthetic success in mandibular first molars with asymptomatic irreversible pulpitis. In this randomized controlled trial, 70 patients were randomly divided into 2 groups (n = 35). Each patient in the control group received only a standard IANB injection of 1.8 mL of 2% lidocaine with 1:100,000 epinephrine. The injection was administered within 1 minute, using a standard aspirating dental cartridge fitted with a 27-gauge dental needle. In the intervention group, 15 minutes after injection of the standard IANB as described for the control group, each patient received a standard MINB injection of 1 mL of 2% lidocaine containing 1:100,000 epinephrine, administered by an operator not involved in assessing the outcomes. After the MINB injection, the patient applied firm finger pressure to the soft tissue of the mental foramen region for 1 minute using the hand on the side opposite to the injection. Objective assessment of tooth anesthesia was carried out with electric pulp tests (EPTs). In addition, the patients rated their pain during the initial steps of endodontic treatment based on a visual analog scale (VAS). The Mann-Whitney U and Wilcoxon tests were used for the analysis of data. Of the 35 patients in each group, 20.0% (7 patients) in the control group and 71.4% (25 patients) in the intervention group had no response to EPTs 15 minutes after injections; this difference was statistically significant (P < 0.05). The VAS pain scores were significantly higher in the control group than in the intervention group (P = 0.001). The administration of MINB with pressure following IANB significantly improved the success of anesthesia in mandibular first molars with asymptomatic irreversible pulpitis.

Methylation status of interleukin-6 gene promoter in patients with Behçet's disease / Estatus de la metilación del promotor del gen interleucina-6 en pacientes con síndrome de Behçet

BACKGROUND: IL-6 mRNA expression is significantly high in many autoimmune diseases such as Behçet's disease; this is often related with more aggressive phenotypes. Nevertheless, the essential molecular process for its high expression has not been completely realized. The aim of this study was undertaken to estimate the gene copy number variation and promoter methylation to IL-6's high expression. METHODS: This study was performed on 51 patients and 61 healthy controls. Initially, DNA and RNA were extracted from all specimens. Promoter methylation levels of IL-6 were evaluated by MeDIP-qPCR technique. Also, IL-6 gene expression was measured by Real-time PCR. After that, we evaluated the relationship between gene expression and methylation, as well as their relationship with clinical specification. RESULTS: As we expected, the expression level of IL-6 gene increased significantly in the patient group compared to the healthy subjects. Also, the relative promoter methylation level of the IL-6 mRNA was significantly lower in patient group compared to healthy group (p < 0.001). DISCUSSION: We disclosed that the promoter hypomethylation may be considered as one of the main defects for IL-6 mRNA high expression in patients with Behçet's disease

ANTECEDENTES: La expresión de ARNm de IL-6 es significativamente elevada en muchas enfermedades autoinmunes, tales como el síndrome de Behçet, y ello se relaciona a menudo con fenotipos más agresivos. Sin embargo, no se ha comprendido plenamente el proceso molecular esencial para esta expresión elevada. El objetivo de este estudio fue la estimación de la variación del número de copias del gen, y la metilación del promotor de la expresión elevada de IL-6. MÉTODOS: Este estudio se realizó en 51 pacientes y 61 controles sanos. Al inicio, se extrajo ADN y ARN de todas las muestras. Se evaluaron los niveles de metilación del promotor de IL-6 mediante la técnica MeDIP-qPCR. También se midió la expresión del gen IL-6 mediante PCR a tiempo real. Tras ello, evaluamos la relación entre la expresión del gen y la metilación, así como su relación con la especificación clínica. RESULTADOS: Según lo previsto, el nivel de expresión del gen IL-6 se incrementó significativamente en el grupo de pacientes, con respecto a los sujetos sanos. También encontramos que el nivel relativo de metilación del promotor de ARNm de IL-6 fue considerablemente menor en el grupo de pacientes, con respecto al grupo sano (p < 0,001). DISCUSIÓN: Concluimos que la hipometilación del promotor puede considerarse uno de los defectos principales de la expresión elevada de ARNm de IL-6, en los pacientes con síndrome de Behçet

Promoter methylation of Bax and Bcl2 genes and their expression in patients with Behcet's disease.

BCL2 and BAX genes are a group of signalling inducer and inhibitor genes playing a key role in the process of cellular physiological death (apoptosis). These genes, through the JAK/STAT signalling pathway, affect different cytokines on cell function and subsequently lead to the pathophysiology of diseases, especially autoimmune diseases. In addition, altering the methylation of genes can affect their expression. Since the aetiology and pathology of Behcet's disease is not fully understood, the aim of this study was to determine the methylation pattern of BCL2 and BAX genes in patients with Behcet's disease and compare it with those of control group. This was a case-control study on 51 patients with Behcet and 61 control subjects. Blood samples were received from all subjects. Subsequently, the peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll method and the methylation of the sites was investigated using quantitative methylation specific PCR (qMS-PCR) technique after extraction of DNA by salting out method and its examination with Nano drop. The results of methylation and expression of Bax gene suggest that the methylation level in the patient group significantly increased compared to the healthy individuals (p-value < .05). Furthermore, the results related to Bax gene expression revealed that the mean of gene expression in the patient group has decreased compared to the healthy group, and this decrease was statistically significant (p-value < .05). The rate of expression and methylation of Bcl2 did not indicate any change in the two patient and healthy groups. Given the results of this study, it can be guessed that perhaps DNA methylation is involved in certain conditions of the disease and it may result in regulation of the expression of the involved genes such as Bax gene, in the pathogenesis of the disease.

Mediterranean fever (MEFV) gene profile and a novel missense mutation (P313H) in Iranian Azari-Turkish patients.

BACKGROUND: Familial Mediterranean fever (FMF) is common in Azari-Turkish people, one of the biggest ethnic groups in Iran. In this study, we sought to investigate the mutation spectrum of the MEFV gene and any genotype-phenotype correlations. METHODS AND MATERIALS: 400 unrelated Azari-Turkish FMF patients were analyzed in this study. Mutations in exons 2, 3, 5, and 10 of the MEFV gene were investigated using direct Sanger sequencing, and their correlations with the clinical features of the patients were analyzed. RESULTS: At least one mutation was detected in 248 (62%) patients. The most common mutations were M694V (26.25%) and E148Q (24.75%), respectively. Abdominal pain (65.2%) and fever 204 (51%) were the most frequent clinical problems in all subjects. The analysis recognized a novel missense mutation in the coding region of the MEFV gene, named P313H, which is the first report of a new mutation in exon 2 of the MEFV gene in an Azari-Turkish family. CONCLUSION: Genotype-phenotype correlations obtained from this study would be helpful in the diagnosis and management of FMF patients in clinical situations. This novel missense mutation may provide useful evidence for further studies of FMF pathogenesis.

Methylation status of interleukin-6 gene promoter in patients with Behçet's disease.

BACKGROUND: IL-6 mRNA expression is significantly high in many autoimmune diseases such as Behçet's disease; this is often related with more aggressive phenotypes. Nevertheless, the essential molecular process for its high expression has not been completely realized. The aim of this study was undertaken to estimate the gene copy number variation and promoter methylation to IL-6's high expression. METHODS: This study was performed on 51 patients and 61 healthy controls. Initially, DNA and RNA were extracted from all specimens. Promoter methylation levels of IL-6 were evaluated by MeDIP-qPCR technique. Also, IL-6 gene expression was measured by Real-time PCR. After that, we evaluated the relationship between gene expression and methylation, as well as their relationship with clinical specification. RESULTS: As we expected, the expression level of IL-6 gene increased significantly in the patient group compared to the healthy subjects. Also, the relative promoter methylation level of the IL-6 mRNA was significantly lower in patient group compared to healthy group (p<0.001). DISCUSSION: We disclosed that the promoter hypomethylation may be considered as one of the main defects for IL-6 mRNA high expression in patients with Behçet's disease.

Value of early rest myocardial perfusion imaging with SPECT in patients with chest pain and non-diagnostic ECG in emergency department.

Evaluation of atypical presentation of angina chest pain in emergency department is difficult. Hospitalization of this patient may impose additional costs and waste the time, early discharge may lead to miss the patients. The aim of this study was to determine volubility of Single Photon Emission Computed Tomography (SPECT) in management of patients admitted to emergency department with atypical manifestations of angina pain, un-diagnostic Electrocardiogram (ECG) and negative enzyme. Half of 100 patients admitted to emergency department with atypical chest pain and un-diagnostic ECG who were candidate for admission, underwent ECG gated resting SPECT. According to the results of SPECT, low risk patient discharged after negative stress SPECT. All discharged patients were followed up for major cardiac events (cardiac death, nonfatal myocardial infarction and repeat admission for congestive heart failure) for 12 months. According to rest SPECT Myocardial Perfusion Imaging (MPI), about 70% of patients in case group was low risk and 30% of them had moderate or high risk. Case group represented lower hospitalization rate and lower need for Coronary Artery Angiography (CAG) in comparison with control group. Mean cost in case group was significantly lower than control group (175.15$ vs. 391.33$, P < 0.001). In one year follow- up no cases of mortality or major cardiovascular events as cardiac infraction were found in discharged patients in case group. our study showed that rest SPECT fulfillment in admitted patients in emergency department was validated method for assessing patients' risk which avoids unnecessary hospitalizations and additional costs.

Analysis of Methylation and Expression Profile of Foxp3 Gene in Patients with Behçet's Syndrome.

Forkhead box P3 (Foxp3) gene is an important means in the Treg cells function, in both maintenances of immune tolerance and regulation of response. Epigenetic modifications of the foxp3 gene at its regulatory regions control the chromatin accessibility for the transcription factors and other transcriptional regulators in order to control Foxp3 expression. In addition, the methylation status of CpG islands within the Foxp3 promoter and regulatory elements regulate the expression of Foxp3. This study was performed to assess the role of the foxp3 gene in patients with Behçet's syndrome (BS). Venous blood samples were collected from all participants and peripheral blood mononuclear cells (PBMC) were extracted through Ficoll-Hypaque method. Genomic DNA was randomly sheared by sonication and immunoprecipitated with a monoclonal antibody. The status methylation of the foxp3 gene was estimated in 108 blood samples of active BS patients and healthy individuals (controls); using methylation DNA immunoprecipitation (MeDIP) technique. Expression analysis was carried out; using Real-time PCR. The expression of foxp3 gene in the patients' group (mean±SD: 1.79±1.12) was significantly lower than the healthy group (mean±SD: 2.73±1.33) (p<001). Also, the methylation levels of Foxp3 promoter showed that its level in patients (mean±SD: 2.3±1.16) was higher than the healthy group (mean±SD: 1.85±0.59). However, this increase was not statistically significant (p>0.05). Also, these results indicated that increasing the amount of methylation of the foxp3 gene by reducing its expression leads to an increase and intensifying of the disease. The decrease in Foxp3 expression is possibly associated with hypermethylation of the gene, and it can be considered as a risk factor for BS. Future studies may be needed to identify the capability of specific DNA methylation alterations in this syndrome.

Hypermethylation of IL-10 gene is responsible for its low mRNA expression in Behçet's disease.

Interleukin-10 (IL-10), produced generally by monocyte, T helper type 2 (Th2), and regulatory T cells (Treg), plays a central role in controlling inflammatory responses and regulating the immune response of the IL-10 mRNA expression. It is significantly down-regulated in many autoimmune diseases such as Behçet's disease; this is mostly associated with more aggressive complications. Nevertheless, the essential molecular process for its low expression has not been completely realized. The aim of this project was attempted to estimate the gene expression, promoter methylation, and protein levels to IL-10's down-regulated expression. In this study, blood samples from 51 (4 missed) patients and 63 (2 missed) healthy controls were taken, with the mononuclear cells isolated by the Ficoll Protocol. DNA and RNA were then subsequently extracted. Promoter methylation levels were evaluated by MeDIP-qPCR. Following this, the extracted RNA was converted to cDNA using the RT-PCR method, with the expression of IL-10 later evaluated by Real-time PCR. And then, serum levels of IL-10 were measured using ELISA method. As we expected, the expression level of the IL-10 gene was seen to significantly decline in the patient group in comparison to the control. Also, the rate of promoter methylation was significantly higher in the IL-10 mRNA low expression group (patient group) compared to its high expression group (healthy group) (P < 0.001). We revealed that hypermethylation of promoter region was the principal defect for the IL-10 mRNA low expression in patients with Behçet's disease.

The Effect of a Mineralized Bone Graft on the Surface Microhardness of Mineral Trioxide Aggregate and Biodentine.

INTRODUCTION: This study was designed to determine the effect of Osteon II mineralized bone powder on the surface microhardness of two retrofilling materials: Mineral trioxide aggregate (MTA) and Biodentine (BD). METHODS AND MATERIALS: Each retrograde material was mixed and carried into 30 sterile custom-made plastic cylinders. Half of the samples in each group were exposed to Osteon II. All cylinders were submerged in simulated tissue fluid and incubated at 37°C and 100% relative humidity for 7 days. Surface microhardness values of each study group was attained using Vicker's microhardness test. The data were analyzed statistically using two-way ANOVA and independent t test at a significance level of 0.05. RESULTS: In all the setting conditions, BD had significantly greater surface microhardness than MTA (P<0.001). Surface microhardness of both materials was significantly reduced in the presence of osteon II (P=0.006 for BD and P<0.001 for MTA). CONCLUSION: Mineralized bone graft materials negatively affect surface microhardness of both MTA and BD. In presence of osteon II, BD had the highest surface microhardness.

Synergistic Anticancer Effects of Silibinin and Chrysin in T47D Breast Cancer Cells

Objective: Breast cancer is one of the most significant causes of female cancer death worldwide. Although several chemotherapeutics have been developed to treat this type of cancer, issues remain such as low survival rates and high reoccurrence after chemotherapy and radiotherapy. To explore a chemopreventive approach to enhancing breast cancer treatment efficacy, the antiproliferative effects of a combination of chrysin and silibinin, two herbal substances, in T47D breast cancer cells were assessed. Materials and Methods: Cytotoxicity of the agents singly and in combination was evaluated by MTT assay. Also, qRT-PCR was used to measure the expression levels of hTERT and cyclin D1 genes after 48 h treatment. Results: Cell viability assays revealed that chrysin or silibinin alone inhibited proliferation in a dose and time-dependent manner, and combining the drugs synergistically induced growth inhibition in the breast cancer cell line. The precise nature of this interaction was further analyzed by the median-effect method, where the combination indices (CI) were <1 for combination treatments, indicating synergism regarding T47D cell proliferation. qPCR results showed that the drug combination also synergistically down-regulated the mRNA levels of hTERT and cyclin D1 at all used concentrations compared with the drugs used alone after 48 h treatment (P ≤ 0.05). Conclusion: The data provide evidence that synergistic antiproliferative effects of Chrysin and Silibinin are linked to the down-regulation of cyclin D1 and hTERT genes, and suggest that their combination may have therapeutic value in treatment of breast cancer.