The relationship of promoter methylation of calcium voltage-gated channel alpha 1 and interleukin-16 to primary osteoarthritis.

OBJECTIVE: Osteoarthritis is the most prevalent joint disease worldwide and the primary cause of musculoskeletal dysfunction. Epigenetic changes in various genes, particularly methylation, have been implicated as possible underlying causes of primary osteoarthritis. The aim of our study was to investigate the promoter methylation status of the calcium voltage-gated channel alpha 1 subunit G (CACNA1G) and interleukin-16 (IL-16) genes, which are strongly associated with calcium channel activity and antigen presentation, respectively, in primary osteoarthritis patients. PATIENTS AND METHODS: Twenty-one patients with primary osteoarthritis and 25 healthy controls were included in our study. The methylation status of CACNA1G and IL-16 genes was analyzed with methylation-specific Polymerase Chain Reaction (PCR), and the serum levels of IL-16 were determined with Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS: The age of the patients was 63.95±8.41 years, and they were 15 females and 6 males. The promoter of the CACNA1G gene was found to be hypermethylated in primary osteoarthritis patients (p<0.001). In contrast, the promoter of the IL-16 gene was found to be hypomethylated compared to the control (p<0.001). The serum levels of IL-16 increased in parallel with the hypomethylated promoter status of IL-16 gene in primary osteoarthritis patients compared to the control (p<0.001). CONCLUSIONS: Our study indicates that the methylation status of CACNA1G and IL-16 gene promoters are epigenetically altered in patients with primary osteoarthritis. Moreover, increased serum IL-16 levels in osteoarthritis patients may be associated with hypomethylation of the IL-16 gene promoter.

Serum irisin levels in colorectal cancer patients.

OBJECTIVE: There are limited studies investigating the role of irisin in colorectal cancer, and the results are diverse. The role of irisin in colorectal cancer patients was investigated in this study. PATIENTS AND METHODS: This cross-sectional study included 53 patients diagnosed with colorectal cancer (CRC) and 87 healthy volunteers. Serum irisin, glucose, insulin, C-peptide, and whole blood hemoglobin A1c (HbA1c) levels were measured in venous blood samples taken from patients and the control group. RESULTS: The mean serum irisin levels were significantly lower in the patient group (23.97 ± 16.94 ng/mL) than in the control group (32.71 ± 17.26 ng/mL) (p = 0.004). Serum glucose levels were 96.58 ± 15.12 mg/dL in the patient group and 81.91 ± 11.24 mg/dL in the control group. Serum glucose levels were significantly higher in the patient group than in the control group (p < 0.01). In the patient group, there was no statistically significant difference between metastasis (+) patients and metastasis (-) patients in terms of serum irisin levels (27.53 ± 18.48 ng/mL and 21.23 ± 15.43 ng/mL, respectively; p = 0.182). CONCLUSIONS: Our study has provided new insights into the potential role of irisin in CRC. However, further studies, including in vitro, in vivo, and larger patient groups, are necessary to fully understand the potential of irisin as a biomarker or therapeutic target for CRC and other diseases.

The promoter methylations of the autoimmune regulator (AIRE) gene and matrix metalloproteinase-3 (MMP-3) gene may have a role in gestational diabetes mellitus.

OBJECTIVE: Gestational diabetes mellitus (GDM) is characterized by new-onset glucose intolerance and is most common in the second and third trimesters of pregnancy. Epigenetic modifications regulate glucose and its cellular interactions with metabolic pathways. Emerging evidence suggests that epigenetic changes contribute to the pathophysiology of GDM. Since these patients have high glucose levels, the metabolic profiles of the fetus and the mother can affect these epigenetic changes. Therefore, we aimed to examine the potential alterations in the methylation profiles of three gene promoters: the autoimmune regulator (AIRE) gene, matrix metalloproteinase-3 (MMP-3), and calcium voltage-gated channel subunit alpha1 G (CACNA1G). PATIENTS AND METHODS: A total of 44 patients diagnosed with GDM and 20 controls were involved in the study. DNA isolation and bisulfite modification were performed from peripheral blood samples of all patients. Then, the promoter methylation status of the AIRE, MMP-3, and CACNA1G genes was determined by methylation-specific polymerase chain reaction (PCR) methylation-specific (MSP). RESULTS: Our results demonstrated that the methylation status of AIRE and MMP-3 changed to unmethylated in the GDM patients compared to healthy pregnant women (p<0.001). However, CACNA1G promoter methylation status failed to show a significant change between experimental groups (p>0.05). CONCLUSIONS: Our results indicated that AIRE and MMP-3 are the genes affected by epigenetic modification, which could be one of the causes of the long-term metabolic effects in maternal and fetal health and can be a target for prevention, diagnosis, or treatment for GDM in future studies.

An investigation of the relationship between rheumatological diseases and soluble receptor for advanced glycation end products.

OBJECTIVE: Soluble receptor for advanced glycation end products (sRAGE) is one of the forms of RAGE. It is a trap receptor that has a role in inhibiting pro-inflammatory processes that will occur with the combination of RAGE and its ligands. Our study aims to examine the level of sRAGE in rheumatological inflammatory diseases and its relationship with these diseases. PATIENTS AND METHODS: A total of 60 patients with Behçet's disease (BD), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and 22 healthy control individuals were included in the study. Comorbidity status, sRAGE levels, disease activity scores, demographic and laboratory data of the patients were recorded. Serum sRAGE levels in these diseases and healthy controls were determined by Enzyme-Linked Immunosorbent Assay (ELISA) kit spectrophotometrically. RESULTS: Serum sRAGE levels in the patient groups were significantly higher when compared to the healthy control group (p < 0.001 for all). On the other hand, when the patient groups were compared with each other in terms of sRAGE levels, there was no significant difference (p > 0.05 for all). The serum sRAGE levels were not correlated with C-reactive protein (CRP) levels, erythrocyte sedimentation rate (ESR), and disease activity scores (p > 0.05 for all). CONCLUSIONS: Serum sRAGE levels increased in BD and in other inflammatory rheumatological diseases. However, this increase does not directly correlate with inflammatory markers and disease activity scores. These results suggest that serum sRAGE level may not be used as a biomarker for disease activity in BD and in other rheumatological diseases.

CIITA expression is regulated by histone deacetylase enzymes and has a role in α-synuclein pre-formed fibril-induced antigen presentation in murine microglial cell line.

AIM: Parkinson's disease (PD) is a chronic neurodegenerative disorder related with several genetic and epigenetic factors. In the context of epigenetic factors, histone acetylation is one of the most associated mechanisms with Parkinson's disease progression. This study investigates the effects of the increased histone acetylation on antigen presentation in microglial cells which were induced by pre-formed fibrils of α-synuclein (pFF α-synuclein). METHODS: Parkinson's disease model was created with pFF α-synuclein administration to the BV-2 microglial cells. BV-2 cells were co-treated with CUDC-907 and TMP-195 to increase histone acetylation in the presence of α-synuclein. Antigen representation was evaluated by determining expression levels of major histocompatibility complex-II (MHC-II) and class-II major histocompatibility complex (CIITA). RESULTS: Our results showed that pFF α-synuclein significantly increased MHC-II expression, and that effect was most severe at 6 h of administration of α-synuclein. Increasing histone acetylation via CUDC-907 and TMP-195 enhanced MHC-II levels expression, which was more severe in CUDC-907. Additionally, CIITA expression levels were significantly increased with pFF α-synuclein administration and intensified with the co-treatment of CUDC-907 and TMP-195. Furthermore, pFF α-synuclein caused a time-dependent increase in the IFN-gamma (IFN-É£) and interleukin-16(IL-16) levels, and that increase was potentiated with CUDC-907 and TMP-195. CONCLUSION: Changes in MHC-II and CIITA expression indicate that histone acetylation increases the antigen presentation properties of microglial cells after pFF α-synuclein or histone deacetylase inhibitor (HDACi) administration. Our results show that microglial antigen presentation might have an essential role in the pathology of Parkinson's disease, and α-synuclein likely to play a primary role in this mechanism.

Predictors of successful vaginal birth after a caesarean in women with a previous single caesarean delivery.

OBJECTIVE: The aim of our study was to present our case series of the trial of labor after a caesarean (TOLAC) and determine significant predictors for a successful vaginal birth after a caesarean (VBAC). PATIENTS AND METHODS: Women with previous single caesarean deliveries who underwent TOLAC between January 2016-December 2019 were included in the study (n = 474). All files were analyzed in terms of demographic characteristics, obstetric history, history of index pregnancy and medical characteristics of previous caesarean delivery. For each current pregnancy, we recorded time from the previous delivery, the BISHOP and TOLAC scores at admission, induction of labor, gestational age at delivery, estimated fetal weight, intrapartum characteristics, mode of delivery and intra-operative findings. RESULTS: Among 474 women who had a previous caesarean delivery and gave consent for TOLAC, 216 resulted in a successful vaginal delivery, whereas 258 underwent repeat caesarean delivery. One hundred and seventy-nine women gave up trial of vaginal delivery during labor. The success rate of VBAC after exclusion of caesarean cases due to maternal requests was 73.2%. The induction rate was significantly higher in cases with successful VBAC (40% vs. 29.1%). The risk of uterine rupture was 0.42% in cases with labor induction. ROC analysis showed significant predictive values of the TOLAC score, body mass index (BMI), the number of previous VBACs and the number of previous vaginal deliveries, birth weight and the BISHOP score at admission. CONCLUSIONS: Our data showed us that major determinants for successful VBAC following labor are the BISHOP score at admission, number of previous vaginal deliveries, body mass index, birth weight and the TOLAC score calculated at admission.

Self-awareness of X, Y, and Z generations for dental health: A comparative clinical study.

BACKGROUND AND AIM: Generation defines as a group of people who were born in a same interval of year and shares similar life events at critical developmental stages, values, behaviors, and significant reactions. The aim of this clinical study was to assess self-awareness of dental health of X, Y, and Z generations in Turkey. MATERIALS AND METHODS: Total of 239 individuals were divided into three homogenous groups X Generation (X Gen; n = 80), Y Generation (Y Gen; n = 80), and Z Generation (Z Gen; n = 79) by their date of birth 1965-1980; 1981-2000; 2001-2013, respectively. Self-rated caries status, frequency of tooth brushing, frequency of dental visits, and actual caries status were recorded. Self-awareness was calculated as the extraction of the numbers of actual caries and self-rated caries and coded as △ Caries. RESULTS: Mean Dental caries status was recorded using the number of decayed, missing or filled teeth (dft/DMFT) was 4.92 for X Gen; 4.68 for Y Gen; 3.66/3.51 for Z Gen individuals, respectively. Actual caries and self-rated caries were significantly incompatible with each other in all study groups (<0.001). △Caries were insignificant in X, Y, and Z Generations (>0.05); nevertheless, self-awareness (self-rated caries = actual caries) of Z Gen were found numerically more (23%) compared to other groups. Tooth-brushing habits of all individuals were mostly once-a-day (>0.05). Mean frequency of dental visits were once in a 3.5; 2.9; 1.5 years for X, Y, and Z Gens, respectively. CONCLUSION: There is no significant correlation between frequency of dental visits and self-awareness measures. Oral health education should urgently point out for all generations by dental professionals, media, and governmental authorities including preventive methods, oral hygiene instructions all aimed at preventing caries and raising self-awareness.

The complex microbiome of caries-active and caries-free supragingival plaques in permanent dentition.

BACKGROUND AND AIM: Dental caries is one of the most common diseases seen in the oral cavity in all periods of deciduous, mixed, and permanent dentition. A comprehensive study of the oral microbiome is required to understand its polymicrobial etiology. The aim of this study was to reveal the plaque microbiome of caries-active and caries-free adults. MATERIALS AND METHODS: A total of 52 samples were collected from 26 caries-active patients and 26 caries-free controls. Dental supragingival plaque samples were collected from each subject and the bacterial 16S rDNA, expanded V3-V4 region, was amplified using next generation sequencing. RESULTS: The core microbiome was defined with 235 shared bacteria in genus level, and among all microbiome 14.8% of all bacteria showed significant difference (P < 0.05). The bacteria responsible of caries may be listed as Anaeroglobus, Atopobium, Bifidobacterium, Centipeda, Cryptobacterium, Desulfobulbus, Filifactor, Howardella, Lactobacillus, Leptotrichiaceae (unclassified), Megasphaera, Mycoplasma, Olsenella, Phocaeicola, Propionibacterium, Pseudoramibacter, Scardovia, Schwartzia, Treponema, and Veillonellaceae (unclassified). CONCLUSION: The present study provides comprehensive knowledge of the microbiological etiology of caries in permanent dentition.

Do Ginger Extract, Natural Honey and Bitter Chocolate Remineralize Enamel Surface as Fluoride Toothpastes? An In-Vitro Study.

BACKGROUND: In recent literatures, much attention has been given to natural products for their health benefits. AIMS: In this study, the objective was to measure the efficacy of the ginger-honey-chocolate mixture as the remineralization effect has been shown in the literature previously and to evaluate the individual contributions of this mixture; ginger, natural honey, bitter chocolate separately on remineralization of initial enamel caries lesion. MATERIALS AND METHODS: All specimens were divided into eight groups as: Ginger (Arifoglu®, Turkey) in powder form, (n = 8); Ginger-Honey-Chocolate (n = 8); Natural honey (Balparmak Plateau Blossom Honey®, Turkey) (n = 9); Bitter chocolate (Nestlé®, Switzerland) (n = 8); MI Paste (GC, Japan) (n = 8); Paradontax (Sensodyne, Glaxosmithklein, USA) (n = 9); Pronamel (Sensodyne, Glaxosmithklein, USA) (n = 9); Control (n = 9) groups. Samples were carried out five pH cycles along 7 days at 37°C for each group. During pH cycling, blocks were put in a demineralization (6 h) and a remineralization solution (18 h). The treatment consisted of 1 min. interaction of enamel surfaces with agent/deionized slurries (1:3 w/w) on a daily basis. The surface microhardness (SMH) was determined before and after pH cycling with a Digital Micro-Vickers Hardness Tester (Wilson Wolpert; Europe BV, 401 MVD, Netherlands). Mineral changes were determined by using FluoreCam® and recovery values were calculated as SMHR% and FΔ%, respectively. RESULTS: All groups showed an enhanced remineralization. There was no significant difference in terms of FΔ% (F = 1.223, P = 0.304) and SMHR% (F = 0.709, P = 0.664) between all groups. CONCLUSION: The herbals (ginger, honey, and bitter chocolate) examined in this study gave promising results with a high remineralization potential.

SAHA attenuates rotenone-induced toxicity in primary microglia and HT-22 cells.

Rotenone is an industrial and environmental toxicant that has been strongly associated with neurodegeneration. It is clear that rotenone induces inflammatory and oxidative stress; however, information on the role of histone acetylation in neurotoxicity is limited. Epigenetic alterations, neuroinflammation, and oxidative stress play a role in the progression of neurodegeneration and can be caused by exposure to environmental chemicals, such as rotenone. Histone modifications, such as methylation and acetylation, play an important role in mediating epigenetic changes. Therefore, we here investigated the effects of histone acetylation on rotenone-induced inflammation and oxidative stress in both primary mouse microglia and hippocampal HT-22 cells using the pan-histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA). Our results showed that SAHA suppressed the inflammatory response by decreasing nuclear factor kappa B and inducible nitric oxide synthase expression. Additionally, SAHA inhibited the rotenone-induced elevation of interleukin 6 and tumor necrosis factor α levels in both cell lines. Furthermore, SAHA improved the rotenone-induced antioxidant status by mitigating the decrease in cellular glutathione levels. Additionally, SAHA prevented the rotenone-induced increase in the HDAC activity in microglial and hippocampal HT-22 cells. Together, our results showed that SAHA reduced rotenone-induced inflammatory and oxidative stress, suggesting a role for histone deacetylation in environmental-related neurotoxicity.

Expression of Ring Box-1 protein and its relationship with Fuhrman grade and other clinical-pathological parameters in renal cell cancer.

OBJECTIVE: To determine the relationship between RING-box protein 1 (RBX-1) expression and renal cell carcinoma (RCC) with prognostic factors. METHODS: A total of 88 patients who underwent radical/partial nephrectomy between January 2009 and January 2016 have been included in our study. The age, gender, tumor location, tumor size, and tumor-node-metastasis stage of each patient was evaluated. From the best sections in hematoxylin-eosin stained pathology preparations, tumor histological subtype, Fuhrman nuclear grade, lymphovascular invasion, renal artery/vein invasion, capsule invasion, perirenal fatty tissue invasion, and tumor grade were evaluated. Participants were divided into 2 groups according to Fuhrman grade. Fuhrman grades 1 to 2 comprised Group 1, and Fuhrman grades 3 to 4 comprised Group 2. An immunoreactivity scoring system was used to evaluate RBX-1 expression. RESULTS: Upon examining all histological subtypes together, it was observed that RBX-1 expression was statistically higher in Group 2 compared to Group 1 (P < 0.008). Upon examining clear RCC cases, it was observed again that Group 2 had a higher RBX-1 expression than Group 1 (P < 0.009). RBX-1 expression was not associated with clinical-pathological parameters including tumor grade, lymphovascular invasion, capsule invasion, or perirenal invasion. CONCLUSION: RBX-1 expression is closely associated with a highly important prognostic factor in RCC-Fuhrman grade-and it shows promise as a prognostic marker. Further studies are required to reveal the importance of RBX-1 in RCC prognosis and treatment.

Amelioration of radiation-induced lung injury by halofuginone: An experimental study in Wistar-Albino rats.

To evaluate effects of halofuginone (H) on radiation-induced lung injury (RILI), 60 rats were divided into six groups: Group (G) 1 control, G2 radiotherapy (RT) only, G3 and G4 2. 5 and 5 µg H and G5 and G6 RT + 2.5 and 5 µg H groups, respectively. A single dose of 12 Gy RT was given to both lungs. H was applied intraperitoneally with daily doses, until animals were killed at 6 and 16 weeks after RT. At 6th and 16th weeks of RT, five rats from each group were killed. Lung tissues were dissected for light and electron microscopy. Chronic inflammation, fibrosis and transforming growth factor-beta (TGF)-ß scores of all study groups were significantly different at 6th and 16th week ( p < 0.001). Chronic inflammation, fibrosis and TGF-ß scores of G2 were higher than G5 and G6 at 6th and 16th weeks of RT. At 16th week, fibrosis and TGF-ß scores of G5 were higher than G6 ( p = 0.040 and 0.028, respectively). Electron microscopical findings also supported these results. Therefore, H may ameliorate RILI. The effect of the H was more prominent at higher dose and after long-term follow-up. These findings should be clarified with further studies.

Genetic polymorphisms affecting antioxidant enzymes are present in tympanosclerosis patients.

BACKGROUND: This study investigated genetic polymorphisms affecting the inducible nitric oxide synthase, superoxide dismutase and catalase enzymes in chronic otitis media patients with and without tympanosclerosis, and the role of genetic susceptibility in the disease aetiology. METHODS: A total of 162 patients who underwent surgery for chronic otitis media were divided into two study groups: a tympanosclerosis group and a chronic otitis media group. A third, the control, group comprised 188 healthy volunteers. Venous blood samples were evaluated using reverse transcriptase polymerase chain reaction. RESULTS: There was a significant difference in GG genotype distribution of the -277A>G polymorphism in the NOS2 gene between the tympanosclerosis and control groups (p T) polymorphism in the SOD2 gene (p > 0.05). There were significant differences in the TT genotype distribution of the -21A>T polymorphism in the CAT gene between the tympanosclerosis and control groups, and between the chronic otitis media and control groups (p < 0.05). CONCLUSION: These results suggest that genetic predisposition may play a role in the aetiopathogenesis of tympanosclerosis.

Phosphorus-nitrogen compounds part 27. Syntheses, structural characterizations, antimicrobial and cytotoxic activities, and DNA interactions of new phosphazenes bearing secondary amino and pendant (4-fluorobenzyl)spiro groups.

A number of partly (7-9) and fully (10a-12d, Scheme 1) substituted mono(4-fluorobenzyl)spiro cyclotriphosphazenes was prepared. The structures of the compounds were determined by MS, FTIR, 1D and 2D NMR techniques. The crystal structures of 9, 11b and 12b were verified by X-ray diffraction analysis. In vitro cytotoxic activity of the phosphazenes (10a-12d) against HeLa cervical cancer cell lines was evaluated. Compound 12c was found to be the most effective, as it is a cytotoxic reagent that might activate apoptosis by altering mitochondrial membrane potential. Compounds 10b, 11b and 12b showed very good activity against yeast strains Candida tropicalis and Candida albicans. BamHI and HindIII digestion results demonstrate that the compounds (10a-12a, 10b-12b, 10d-12d), and (9, 10c-12c) bind with G/G and A/A nucleotides, respectively.

Identification of Turkish and standard apple rootstocks by morphological and molecular markers.

Two local (Vezir-1 and Vezir-2) and two standard (M9 and MM106) clonal apple rootstocks were compared using both morphological and molecular markers. International Union for the Protection of New Varieties of Plants criteria were used for morphological evaluation, which did not clearly separate these rootstocks. We tested 47 random decamer primers for random amplified polymorphic DNA analysis; 15 of them gave reproducible polymorphic patterns, yielding 109 bands, which showed 78% polymorphism. Based on a dendrogram obtained by unweighted pair group method using arithmetic average analysis, three clusters were obtained. The highest genetic similarities were found between M9 and Vezir-2 (0.670). The random amplified polymorphic DNA markers proved to be more efficient than the standard morphological markers for the identification of rootstocks.

Boron removal from aqueous solutions by activated carbon impregnated with salicylic acid.

In this study, the removal of boric acid from aqueous solution by activated carbon impregnated with salicylic acid was studied in batch system. pH, adsorbent amount, initial boron concentration, temperature, shaking rate and salicylic acid film thickness were chosen as parameters. Boron removal efficiencies increased with increasing adsorbent amount, temperature and pH, decreasing initial boron concentration. As thickness of salicylic acid film on activated carbon becomes thin up to 0.088nm, the efficiency increased, and then, the efficiency decreased with becoming thinner than 0.088nm of salicylic acid film. Shaking rate was no effect on removal efficiency. In result, it was determined that the use of salicylic acid as an impregnant for activated carbon led to the increase of the amount of boron adsorbed. A lactone ring, being the most appropriate conformation, forms between boric acid and -COOH and -OH groups of salicylic acid.