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Abstract Background Cisplatin, one of the most effective and potent anticancer drugs, is used in the treatment of a wide variety of both pediatric and adult malignancies. However, the chemotherapeutic use of cisplatin is limited by its serious side-effects such as nephrotoxicity and ototoxicity. Cisplatin chemotherapy induces a reduction in the antioxidant status, leading to a failure of the antioxidant defense against free-radical damage generated by antitumor drugs. Cisplatin-induced oxidative stress in the kidney was partially prevented by antioxidant treatments using superoxide dismutase, glutathione, selenium and flavonoids. Melatonin and its metabolites possess free-radical scavenging activity and it has been shown that they protect against cisplatin toxicity. However, the mechanism of the protective effects of melatonin against cisplatin-induced nephrotoxicity is still essentially unknown. We therefore designed this study to investigate the underlying mechanism of the protective effect of melatonin against cisplatin-induced renal damage in a rat nephrotoxicity model in vivo. Methods Twenty eight 8-week-old male Wistar rats were divided into four groups of control, melatonin treatment (4 mg/kg b.w i.p. for 10 days), cisplatin treatment (7 mg/kg b.w., i.p.) and melatonin and cisplatin combination treatment. Serum urea nitrogen (urea-N) and creatinine levels were measured. Histopathological changes were evaluated. In addition, we analyzed the expression levels of HO-1, Nrf2, NF-κB and AP-1 in Western blot analysis. Results Both serum creatinine and urea nitrogen increased significantly following cisplatin administration alone; these values decreased significantly with melatonin co-treatment of cisplatin-treated rats. Histological analysis showed that cisplatin caused damage in the proximal tubular cells in the kidneys of cisplatin-treated rats; these changes were reversed by melatonin co-treatment. Upon Western blot analysis, melatonin treatment increased Nrf2 accumulation in the nuclear fraction, and increased the expression of HO-1 in the cytosolic fraction as compared to the cisplatin-treated rats. Expressions of NF-κB p65 and AP-1 were increased significantly in the kidneys of rats treated with cisplatin compared with the expression in the kidneys from the control, melatonin-only-treated and melatonin co-treated rats. Conclusion Our present data suggest that melatonin attenuates cisplatin-induced nephrotoxicity possibly by modulating Nrf2/HO-1 signaling.

Introduction: Congenital anomalies of the kidney and urinary tract (CAKUT) are characterized by several malformations. Its prevalence is 0.3-0.6% in live births. The B-cell lymphoma ( BCL-2 ) gene regulates apoptosis, and the Leukemia Inhibitory Factor ( LIF ) gene plays a role in many biological processes, such as blastocyst growth and uterine preparation for implantation. In this study, two single nucleotide polymorphisms (SNPs) of the BCL-2 gene (rs2279115 and rs4987856) and one SNP of the LIF gene (rs929271) were investigated in CAKUT patients for the first time., Methods: Hundred and twenty-nine CAKUT patients and 105 controls were enrolled in this study. We used polymerase chain reaction-restriction fragment length polymorphism for rs2279115 and rs929271 and SNaPshot for rs4987856. The χ 2 test was used to compare discrete variables, and the independent sample t test was used to compare continuous variables., Results: The allele frequencies for the rs2279115 and rs4987856 polymorphisms of BCL-2 and the rs929271 polymorphism of LIF were not significantly different between the patient and control groups ( p = 0.162, p = 0.053, p = 0.635, respectively). However, the co-segregation analysis revealed a significant difference in the distribution of allele frequencies between the patient and control groups for two genetic variations: LIF rs929271 SNP and BCL-2 rs4987856 SNP ( p = 0.034). The relative odds ratio was 2.444 (95% Confidence Interval (CI) 1.054-5.671)., Conclusion: This study, which is the first time in the literature, showed that changes in BCL-2 and LIF genes are associated with CAKUT disease., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 S. Karger AG, Basel.)

Objectives: Acute and chronic allograft rejection have been continuously an important obstacle in the follow-up of renal transplant recipients. During clinical management, several factors acting simultaneously result in acute rejection and chronic allograft nephropathy. Matrix metalloproteinases and tissue inhibitors of metalloproteinases are responsible for the organization of the extracellular matrix and play roles in cell proliferation and cellular invasion. Changes in matrix metalloproteinase expression levels have been reported to be associated with renal allograft rejection and interstitial fibrosis. In this study, we aimed to investigate functional polymorphisms of MMP2, MMP9, and TIMP2 genes in pediatric renal transplant recipients., Materials and Methods: Our study included 68 kidney transplant recipients and 58 control patients. The kidney transplant recipient group was further divided into 2 subgroups: no graft rejection (n = 47) and graft rejection (n =21). MMP2 -735C >T (rs2285053), MMP2 -1306C >T (rs243865), MMP2 -1575G >A (rs243866), MMP9 c.-1562C >T (rs3918242), TIMP2 -418G >C (rs8179090), and TIMP2 303C > T (rs2277698) polymorphisms were analyzed with the use of polymerase chain reaction and restriction fragment-length polymorphism methods. Allele prevalence was compared with reference values of the control group, and Hardy-Weinberg equilibrium was tested., Results: Mean ages were 16.7 ± 3.9 years for the study group and 14.8 ± 5.6 years for the control group. The mean follow-up time after transplant was 37.7 ± 7.9 months. We compared allele frequencies in the 2 groups and calculated a statistically significant difference in rs2285053, rs243865, rs243866, rs3918242, rs8179090, and rs2277698 polymorphism frequencies between the transplant recipients and control patients. When the transplant recipient group was compared in itself with regard to allograft rejection, all investigated polymorphisms except TIMP2 -418G >C (rs8179090) revealed a statistically significant difference between those with and without rejection (P < .05)., Conclusions: Matrix metalloproteinases and their tissue inhibitors could be important predictive biological markers for the follow-up of kidney transplant recipients.

Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disorder with recurrent fever, abdominal pain, serositis, articular manifestations, erysipelas-like erythema, and renal complications as its main features. Caused by the mutations in the MEditerranean FeVer (MEFV) gene, it mainly affects people of Mediterranean descent with a higher incidence in the Turkish, Jewish, Arabic, and Armenian populations. As our understanding of FMF improves, it becomes clearer that we are facing with a more complex picture of FMF with respect to its pathogenesis, penetrance, variant type (gain-of-function vs. loss-of-function), and inheritance. In this study, MEFV gene analysis results and clinical findings of 27,504 patients from 35 universities and institutions in Turkey and Northern Cyprus are combined in an effort to provide a better insight into the genotype-phenotype correlation and how a specific variant contributes to certain clinical findings in FMF patients. Our results may help better understand this complex disease and how the genotype may sometimes contribute to phenotype. Unlike many studies in the literature, our study investigated a broader symptomatic spectrum and the relationship between the genotype and phenotype data. In this sense, we aimed to guide all clinicians and academicians who work in this field to better establish a comprehensive data set for the patients. One of the biggest messages of our study is that lack of uniformity in some clinical and demographic data of participants may become an obstacle in approaching FMF patients and understanding this complex disease., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by recurrent attacks of fever and serositis. Diagnosis is made according to clinical findings and supported by genetic analysis. The most commonly used adult diagnostic criteria are the Tel-Hashomer criteria. Pediatric criteria for FMF diagnosis were described in 2009, but their reliability should be supported by additional reports. In this study, we aimed to compare the pediatric criteria and the Tel-Hashomer and 2019 Eurofever/PRINTO classification criteria using our FMF cohort. A total of 113 patients diagnosed with FMF were included. Demographic features and laboratory findings were retrospectively collected from the patients' files. The patients were evaluated with the Tel-Hashomer, pediatric and Eurofever/PRINTO classification criteria. At least two of five new pediatric criteria were as sensitive (89%) and specific (85%) as the Tel-Hashomer criteria (sensitivity 70%, specificity 96%). We also evaluated the Eurofever/PRINTO classification criteria using our cohort and found a sensitivity of 94% and specificity of 91%.   Conclusion: Using pediatric criteria for the diagnosis of FMF in children is a feasible and simple approach that can diagnose the disease based on at least two criteria. Therefore, our study supports the use of pediatric criteria in FMF diagnosis of children. Our results also confirm that the Eurofever/PRINTO classification criteria can be successfully applied for the diagnosis of FMF due to their high sensitivity (94%) and specificity (91%). What is Known: • The FMF diagnosis is made according clinical findings and supported by genetic analysis. • The use of adult diagnostic criteria in pediatric FMF patients is controversial since classical clinical presentation is often absent in children. What is New: • Our study supports both the use of pediatric criteria and Eurofever/PRINTO classification criteria in clinical practice., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: We aimed to investigate the association of vitamin D receptor (VDR) gene TaqI single nucleotide polymorphism (SNPs) with serum lead (Pb) levels in maternal and umbilical cord blood., Materials and Methods: Eighty-one patients who lived in Konya, Turkey for the last 3 years and had delivery at Başkent University Konya Hospital in 2016 were included in this study. Venous blood samples were drawn from each volunteer immediately before giving birth to determine the maternal Pb levels and VDR SNPs. Additionally, umbilical cord blood samples were collected from the umbilical vein into tube with EDTA as an anticoagulant immediately after birth to determine Pb levels of the fetus., Results: The median level of Pb in the maternal blood was 29.00 (Interquartile Range (IQR) = 16.35) μg/L and the median Pb level in the cord blood was 22.50 (IQR = 9.75) μg/L. Blood Pb level of women living in the urban area was significantly higher than in those living in the rural area (Z = 2.118; p = .034). There was a very strong positive correlation between the Pb levels in the maternal blood and in the umbilical cord blood (ρ = 0.825, p < .001, respectively). Regarding VDR SNPs, "TT", "TC", and "CC" VDR TaqI genotypes were observed in 28 (34.6%), 45 (55.5%), and eight samples (9.9%), respectively. Pb levels in maternal and cord blood were higher in women with the "CC" VDR TaqI genotype; however, there was no statistically significant difference (p > .05)., Conclusions: Although women with the "CC" VDR TaqI genotype had higher maternal and cord blood Pb levels, this was statistically insignificant and therefore, VDR TaqI SNPs did not significantly affect maternal and umbilical cord blood Pb levels.

Objective: Fractalkine, member of chemokine family, is involved in many inflammatory processes in the human body. The aim of this study is to compare expression levels of fractalkine ligand and its receptor in chronic tonsillitis and hypertrophic tonsil samples., Methods: The study was conducted at Baskent University Departments of Otorhinolaryngology and Medical Genetics. It is designed as a prospective, non-randomized, controlled clinical study. Total 97 samples, obtained from adenotonsillectomy due to chronic tonsillitis or tonsillar hypertrophy, were participated in the study. Fractalkine and its receptor expression levels were determined and comparison was made between the tissue groups. c.839C>T (T280M) polymorphism of fractalkine receptor was analyzed, then relationship between polymorphism and the expression level of fractalkine receptor was investigated., Results: Fractalkine receptor expression was significantly higher in the hypertrophic tonsil group than chronic tonsillitis group (p<0.05)., Conclusion: Fractalkine, member of chemokine family, and its receptor may play role in preventing chronic-recurrent tonsillitis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Androgenetic complete hydatidiform moles are human pregnancies with no embryos and affect 1 in every 1,400 pregnancies. They have mostly androgenetic monospermic genomes with all the chromosomes originating from a haploid sperm and no maternal chromosomes. Androgenetic complete hydatidiform moles were described in 1977, but how they occur has remained an open question. We identified bi-allelic deleterious mutations in MEI1, TOP6BL/C11orf80, and REC114, with roles in meiotic double-strand breaks formation in women with recurrent androgenetic complete hydatidiform moles. We investigated the occurrence of androgenesis in Mei1-deficient female mice and discovered that 8% of their oocytes lose all their chromosomes by extruding them with the spindles into the first polar body. We demonstrate that Mei1 -/- oocytes are capable of fertilization and 5% produce androgenetic zygotes. Thus, we uncover a meiotic abnormality in mammals and a mechanism for the genesis of androgenetic zygotes that is the extrusion of all maternal chromosomes and their spindles into the first polar body., (Copyright © 2018 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Copper cause oxidative damage in plant cells, and plant extracts are the sources of free radical scavengers. We tested the hypothesis that whether Corchorus olitorius (jute) and Urtica pilulifera (Roman nettle) seed extract treatments of germinated seeds affect copper induced oxidative and genotoxic damage or antioxidant response in tomato. Seedlings were exposed to toxic copper concentration (30 ppm) for 7 days. In one experimental group (treatment 1), extract (100 μg mL -1 ) was added to media. In the other group (treatment 2), tomato seeds were pre-soaked by the extract (100 μg mL -1 ) prior to germination and copper application. Malondialdehyde and endogenous H 2 O 2 levels in the groups treated with extract and copper were significantly lower than that of the untreated groups. Pre-soaking seeds with the nettle extract solution significantly enhanced catalase activity under unstressed condition. Jute treatment also enhanced catalase activity under copper stress. Ascorbate peroxidase activity remained at unstressed level in copper treated groups. Extract treatments significantly decreased copper induced DNA damage in root nuclei. Jute seed extract contained salicylic acid and quercetin which can be correlated with the evoked effects. We demonstrated protective effect of plant extract treatments against copper stress of tomato seedlings prior to germination or during seedling development.

Objectives: Medication-related osteonecrosis of the jaws (MRONJ) is an extremely therapy-resistant disease involving the jaws especially following bisphosphonate treatment. Bisphosphonates accumulate in bone in concentrations sufficient to be directly toxic to the oral epithelium. Current therapeutic options are inadequate for the prevention and treatment of MRONJ. The aim of this study was to investigate effects of ozone gas plasma therapy on wound healing in bisphosphonate-applied human fibroblasts., Material and Methods: Human primary gingival fibroblasts were cultured. Cytotoxic concentrations (IC50) of bisphosphonates (pamidronate (PAM), alendronate (ALN), and zoledronate (ZOL)) were determined by MTT test. A 60 μg/μl for 30 s of ozone gas plasma application was performed to all experimental culture flasks after drug treatment at 24-h intervals as 3 s/cm 2 . Genotoxic damages were evaluated by comet assay and wound healing was determined by in vitro scratch assay., Results: PAM, ALN, and ZOL applications caused genotoxic damage on primary human gingival fibroblast DNA. Ozone gas plasma therapy significantly decreased the genotoxic damage (p < 0.05), and this application provided 25, 29, and 27% less genotoxic damage in order of ALN, PAM, and ZOL groups. Ozone gas plasma therapy significantly increased wound healing rates both in postsurgical 24th and 48th hours for all doses of experimental drug groups (p < 0.05)., Conclusion: The ozone gas plasma application decreased genotoxic damage effect of bisphosphonate usage while improved the wound closure rate on human gingival fibroblasts., Clinical Relevance: Ozone gas plasma therapy may be helpful in prevention of gingival healing delay in MRONJ pathogenesis especially when applied simultaneously with surgical intervention.

Objective: Ficolins are complement activating peptides that play a role in the initial host defense against infectious pathogens. In the present study, we investigated the relationship between single nucleotide polymorphisms (SNPs) in the ficolin 2 gene (FCN2) and chronic adenotonsillitis in pediatric cases., Study Design: Case-control study., Methods: A total of 101 pediatric patients diagnosed with chronic adenotonsillitis and 100 healthy children were enrolled in the study. Genotypes of FCN2 promoter SNPs - 602 G>A and -4 A>G, and the exonic SNP c.772G>T were determined by light SNP assay after realtime PCR analysis using genomic DNA samples obtained from peripheral blood samples of all participants., Results: Of the 101 chronic tonsillitis patients, 38 were girls and 63 were boys; the mean age was 5.2 ± 2.3 years. The c.772G>T SNP frequency was significantly higher in chronic adenotonsillitis cases compared to the control group (p = 0.00); however, no significant difference was determined at positions -602 G>A or -4 A>G (p > 0.05)., Conclusions: The FCN2 c.772G>T genotype appears to be associated with predisposition to chronic adenotonsillitis in the pediatric age group. This nucleotide change is likely to influence the level of gene expression and contribute to the development of disease., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Obstructive sleep apnea syndrome (OSAS) is a public health problem. There is an effort to establish the genetic contributions to the development of OSAS. One is matrix metalloproteinases, extracellular matrix degrading enzymes related to systemic inflammation. However, the impact of matrix metalloproteinase-9 (MMP-9) genotypes on the development of OSAS is unknown. Our aim was to determine whether MMP-9 single nucleotide polymorphism (SNP) (MMP-9 -1562C > T) is related to susceptibility to OSAS., Material and Methods: A total of 106 patients with a history of sleep apnea and 88 controls without a history of sleep apnea were enrolled in this study. Genotypes were determined by restriction fragment length polymorphism analyses after polymerase chain reaction., Results: Genotypes and allele frequencies of the MMP-9 -1562C > T SNP was not statistically different between the patient and control groups (p > 0.05). There was a statistical association between apnea-hypopnea index (AHI) and body mass index (BMI), and also between AHI and neck circumference (p < 0.001). There was no association among the genotypes and AHI, neck circumference, or BMI (p > 0.05)., Conclusions: We found no association between MMP-9 -1562C > T SNP and OSAS. Studies to investigate the role of other polymorphisms and expression of MMP-9 gene will provide more information., (Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Fractalkine (CX3C), a chemokine expressed by epithelial cells within normal and inflamed colorectal mucosa, induces leukocyte adhesion and migration via fractalkine receptor. The aim of this study was to investigate two single nucleotide polymorphisms of the fractalkine receptor gene as a risk factor both for the development and clinical findings of ulcerative colitis. In this study, 51 patients with ulcerative colitis (UC) and 80 controls were recruited. Genotypes of fractalkine receptorc.745G&gt;A (V249I) and c.839C&gt;T (T280M) polymorphisms were identified by restriction fragment length polymorphism analyses after polymerase chain reaction.Genotype distribution and allele frequencies of V249I and T280M were not statistically significantly different between UC and control groups (p&gt;0.05). No statistically significant relationship was found between fractalkine receptor polymorphisms and clinical findings of UC. We observed no significant difference in fractalkine receptor polymorphism between patients and control group and no genotype-phenotype relation. Therefore, we concluded that fractalkine receptor polymorphisms may not contribute to the molecular pathogenesis of UC.

Background: Defensins are antimicrobial peptides expressed on mucosal surfaces. They function as part of the innate immune system. Palatine tonsils play important roles in innate immune system. However, our knowledge on the pathophysiology of chronic tonsils is limited., Objective: The aim of this study was to investigate the association between beta defensin 1 gene single nucleotide polymorphisms and chronic tonsillitis., Study Design: Prospective, non-randomized, controlled clinical study., Setting: Tertiary referral center., Subjects and Methods: Eighty six patients with chronic tonsillitis and eighty controls without history of chronic tonsillitis were enrolled in this study. Genotypes were determined by restriction fragment length polymorphism analyses after polymerase chain reaction., Results: Genotype and allele frequencies of the -20G/A (rs11362), -44C/G (rs1800972) and -52G/A (rs1799946) single nucleotide polymorphisms were not statistically different between patients and control groups (p>0.05)., Conclusion: In this study, we found that DEFB1 gene -20G/A, -44C/G and -52G/A single nucleotide polymorphisms were not associated with chronic tonsillitis. Studies, which analyse other polymorphism of the beta defensin 1 gene in large case series, should be conducted to understand the role of DEFB1 gene on chronic tonsillitis., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Context: Propranolol, atenolol, and ICI118,551 are non-selective β-adrenergic receptor (AR), β1-AR, and β2-AR antagonists, respectively., Objective: We investigated the efficacy of propranolol, atenolol, and ICI118,551 on proliferation, migration, and invasion of non-stimulated breast (MCF7), colon (HT-29), and hepatocellular (HepG2) cancer cells., Materials and Methods: β-AR expression profiling of cells was performed by real time PCR. Cell proliferation was determined by MTT. Boyden chamber and scratch assays were performed to evaluate invasion and migration., Results and Discussion: All cell lines expressed β-ARs. ICI118,551 was the most cytotoxic, whereas atenolol was the least effective β-AR antagonist for 24, 48, and 72 h. Cell invasion was inhibited by ICI118,551 (45, 46, and 50% for MCF7, HT29, and HepG2, respectively) and propranolol (72, 65, and 90% for MCF7, HT29, and HepG2, respectively). Propranolol, atenolol, and ICI118,551 reduced migration of MCF7, HT-29, and HepG2 cells to varying extents depending on the application concentration and duration. Propranolol and atenolol reduced migration of MCF7 and HT-29 in a concentration-dependent manner, whereas migration of these cells decreased after 48 and 72 h of ICI118,551 applications., Conclusion: Beta2-AR antagonist seemed to be the most cytotoxic β-blocker on non-stimulated cancer cells. Propranolol and ICI118,551 were more effective than atenolol in inhibiting invasion and migration of non-stimulated MCF7 and HT-29 cells; ICI118,551 being the most potent. Concordantly, β2-selective blockage seemed to be more effective for non-stimulated cells. Effect of the selective β-AR antagonists showed variation depending on the concentration, incubation time, and histological origin of cells.

We describe a case of blastoid mantle cell lymphoma with a complex karyotype. The blastoid variant is a rare type of non-Hodgkin lymphoma exhibiting an aggressive clinical course. Mantle cell lymphoma is a distinct entity of mature B-cell neoplasms genetically characterized by the presence of t(11;14). In the present case, conventional analysis revealed structural abnormalities of chromosomes 2, 4, 6, 10, 13, and 19, along with 3 additional marker chromosomes. The derivative 1 chromosome determined in the case was a result of t(1p;11q). Our interesting finding was the presence of a different translocation between 11q and chromosome 1 in addition to t(11;14). Thus, the resulting 11q duplication was believed to additionally increase the enhanced expression of cyclin D1 gene, which is responsible in the pathogenesis of the disease. Fluorescence in situ hybridization method by the t(11;14) probe revealed clonal numerical abnormalities of chromosomes 11 and 14 in some cells. The detection of multiple abnormalities explains the bad prognosis in the present case. On the basis of our findings, we can easily conclude that results of cytogenetic analyses of similar mantle cell lymphoma patients would provide clues about new responsible gene regions and disease prognosis. In conclusion, it has been suggested that the presence of multiple chromosomal aberrations in addition to the specific t(11;14) may have a negative impact on clinical course and survival rate.

The objective of this study is to examine whether there is an association of fractalkine gene receptor polymorphisms with chronic tonsillitis. This is a cross-sectional study in the setting of a tertiary referral center. The study group included 79 patients with chronic tonsillitis and 76 controls without history of chronic tonsillitis. Genotypes were identified by restriction fragment length polymorphism analyses after polymerase chain reaction. c.745G>A (V249I) single nucleotide polymorphism and the frequencies of the G and A alleles did not differ in the patient and control groups (p = 0.363; p = 0.743, respectively). c.839C>T (T280M) single nucleotide polymorphism was found to be higher in controls than in the patients with chronic tonsillitis (p < 0.001). Consistent with this result, T allele frequency was higher in controls than in the patients with chronic tonsillitis (p < 0.001). In this study, we suggested that fractalkine gene receptor c.839C>T (T280M) single nucleotide polymorphism could be associated with a reduced risk of chronic tonsillitis.

Objective: Pelvic organ prolapse (POP) is a common disorder that negatively impacts the quality of life in many women. Uterosacral ligaments (USLs) are supportive structures of the pelvic organs that are often attenuated in women with POP. The HOXA genes regulate the development of the uterosacral ligaments. We compared expression of HOXA11 and MMP2 in USLs of women with and without POP., Material and Methods: A prospective sequential cross sectional study was conducted in ZTB Women's Health Research and Education Hospital. We compared expression of HOXA11 and MMP2 in USLs of women with (n:18) and without (n: 15) POP. Total RNA was isolated from patient (n:18) and control (n:15) uterosacral ligament tissues with TriPure isolation reagent according to the manufacturer's instructions. Expression levels of HOXA11 and MMP2 were determined using semiquantitative RT-PCR in a Light Cycler 480 system. Real-time ready catalog assays, which are short FAM-labeled hydrolysis probes containing locked nucleic acid, were used for RT-PCR reactions., Results: There was no difference in patients' mean age, parity, body mass indexes, and menopausal status between two groups. Means of RNA expression of MMP2 were 1.27±0.6 and 0.75±0.4 in the POP group vs control group, respectively (p:0.007). Means of RNA expression of HOXA 11 were 2.57±2.4 and 1.94±1.4 in the POP group vs control group, respectively (p:0.376). The POP group was divided as mild and severe POP; there was no difference in HOXA11 and MMP2 RNA expression between groups (p>0.05)., Conclusion: Although there was no difference HOXA11 RNA expression in USLs with the POP group vs control, there was a significant difference MMP2 RNA expression in USLs with the POP group vs control. There are limited studies on this subject, and study results are contradictory. Further investigations with larger numbers of cases are needed to clarify this subject.

Objectives/hypothesis: To achieve injectable tissue-engineered cartilage using a commercially available fibrin sealant, and to determine the most suitable fibrin glue concentration, cartilage source, and cultured chondrocyte concentration., Study Design: Animal research., Methods: A total of 28 immunocompetent New Zealand white rabbits were divided into four groups. The cultured chondrocytes from different anatomical sources carried in fibrin glue with and without aprotinin in different concentrations of fibrinogen and thrombin (Tisseell), were injected into forehead and interocular regions of the rabbits. The new tissue formation was harvested at 8 weeks and analyzed through gross and histological analysis., Results: The new tissue formations were found in round, elliptical, and flat forms. The mean value of Tisseell and cell suspension was 0.8 cc in all of the rabbits' injection regions, but the mean volume of the samples in which immature cartilage matrix and mature cartilage was 0.1 cc. In the 20 of the 55 injection regions of rabbits (36, 36%), mature and/or immature cartilage formation were observed. We observed inflammatory reactions, abscess formation, and foreign body reactions around the new cartilage tissue of tissue-engineered cartilage. The comparison of results using different cartilage sources, chondrocyte concentrations, or different fibrin glue concentrations did not show any significant difference., Conclusions: We observed that changing the concentrations of ingredients of commercially available fibrin glue, the source of the cartilage, or the cultured chondrocyte concentration did not have significant effect on neocartilage formation., (Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.)

Hepatocellular carcinoma (HCC) is one of the rare tumors with well-defined risk factors. The multifactorial etiology of HCC can be explained by its complex molecular pathogenesis. In the current study, the methylation status of 7 genes involved in DNA repair mechanisms, namely MLH1, PMS2, MSH6, MSH2, MGMT, MSH3, and MLH3, was investigated in tumor samples from HCC patients, using the methylation-specific-multiplex ligated probe amplification method and the results were correlated with available clinical findings. The most common etiological factor in these cases was the presence of hepatitis B alone (47.2%). Among the 56 cases that were studied, promoter methylation was detected in at least one of the genes in 27 (48.2%) cases, only in 1 gene in 13 (23.2%) cases, and in >1 gene in 14 (25%) cases. Of the 7 genes investigated, methylation was most frequently observed in MSH3, in 14 (25%) cases. Methylation of at least 1 gene was significantly more frequent in patients with single tumors than multifocal tumors. There were significant differences regarding hepatitis B status, Child Class, tumor number, grade, and TNM stage in cases where PMS2 methylation was detected. Our results suggest that methylation of genes involved in mismatch repair may be responsible in the pathogenesis of HCC, and evaluating changes in multiple genes in these pathways simultaneously would be more informative. Despite being a robust and relatively inexpensive method, the methylation-specific-multiplex ligated probe amplification assay could be more extensively applied with improvements in the currently intricate data analysis component.

Context: Corchorus olitorius L. (Malvaceae) has industrial importance in world jute production and is a widely cultivated and consumed crop in Cyprus and in some Arabic countries., Objective: The present study investigated cytotoxic and genotoxic effects of leaf extracts (LE) and seed extracts (SE) of the C. olitorius on the multiple myeloma-derived ARH-77 cells. The extracts were also evaluated for their total phenol content (TPC) and free radical scavenging activity (FRSA)., Materials and Methods: C. olitorius was collected from Nicosia, Cyprus. TPC and FRSA were measured by Folin-Ciocalteu and DPPH free radical methods, respectively. Cytotoxicity was evaluated by the MTT assay (4-2048 µg/mL range), and DNA damage (at IC50 and ½IC50) was measured by the comet assay., Results and Discussion: The LE had significantly higher total phenol (78 mg GAE/g extract) than the SE (2 mg GAE/g extract) with significantly higher FRSA (IC50 LE: 23 µg/mL and IC50 SE: 10 401 µg/mL). Both LE and SE exerted cytotoxic effects on cells after 48 h. The IC50 of SE (17 µg/mL) was lower than LE (151 µg/mL), which demonstrates its higher cytotoxicity on cells. The extracts were applied at 150 and 75 µg/mL for LE and at 17 and 8.5 µg/mL for SE, and the results of the comet assay revealed that the extracts induced genotoxic damage on ARH-77 cells. In both 48 h leaf and seed extract treatments, genotoxic damage significantly increased with increasing concentrations at relevant cytotoxic concentrations., Conclusion: To our knowledge, this is the first report demonstrating the high cytotoxic potential of C. olitorius SE and the genotoxic potential of LE and SE.

The aim of this study was to comparatively evaluate antibacterial activities of methanol (MetOH) and aqueous (dw) leaf (L), root (R) and seed (S) extracts of Urtica dioica L. (Ud; stinging nettle) and Urtica pilulifera L. (Up; Roman nettle) on both food- and plant-borne pathogens, with total phenolic contents and DPPH radical scavenging activities (DRSA). MetOH extracts of leaves and roots of U. dioica had the highest DRSA. Extracts with high antibacterial activity were in the order Up-LMetOH (13/16) > Ud-SMetOH (11/16) > Up-SMetOH (9/16). Results obtained with Up-SMetOH against food spoiling Bacillus pumilus, Shigella spp. and Enterococcus gallinarum with minimum inhibitory concentrations (MICs) in 128-1024 μg/ml range seem to be promising. Up-SMetOH also exerted strong inhibition against Clavibacter michiganensis with a considerably low MIC (32 μg/ml). Ud-SMetOH and Up-LMetOH were also effective against C. michiganensis (MIC = 256 and 1024 μg/ml, respectively). Ud-SMetOH and Ud-RMetOH had also antimicrobial activity against Xanthomonas vesicatoria (MIC = 512 and 1024 μg/ml, respectively). Results presented here demonstrate high-antibacterial activity of U. pilulifera extracts and U. dioica seed extract against phytopathogens for the first time, and provide the most comprehensive data on the antibacterial activity screening of U. pilulifera against food-borne pathogens. Considering limitations in plant disease control, antibacterial activities of these extracts would be of agricultural importance.

Numerical abnormalities of sex chromosomes are seen approximately 1 in 400 live births. Pentasomy X is a very rare chromosomal abnormality and it is defined as presence of five X chromosomes instead of two. Prenatal sonographic features have rarely been described in the literature before. Here we present a non-immune fetal hydrops diagnosed during the 17th week of gestation. Ultrasonographic examination revealed subcutaneous edema, pleural effusion and ascites, and also clinodactyly of the fifth fingers of both hands. The fetal karyotype was assessed as 49,XXXXX (pentasomy X) in two different culture flasks. Hydropic signs regressed at 21 weeks' gestation. Prenatal diagnosis may not be possible usually for this rare chromosomal abnormality. Every anomaly detected prenatally, such as transient hydrops, may help us to diagnose pentasomy X., (© 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.)

Background: Cytogenetic, molecular and epigenetic changes are all known to take place in the pathogenesis of meningiomas. In this study, we aimed at investing methylation of MGMT (DNA repair), CDKN2A (cell cycle control), GSTP1 (detoxification), and THBS1 (angiogenesis inhibitor) genes, which are known to be unmethylated in normal tissue, in meningioma samples., Materials and Methods: Methylation specific polymerase chain reaction was used to study promoter regions methylation of genes in 36 patient samples., Results: Methylation in promoter regions of MGMT, CDKN2A, GSTP1, and THBS1 genes were found in 11.1%, 8.3%, 2.8%, and 0% of the cases, respectively. About 19.4% of cases revealed promoter methylation of at least a single gene, whereas only 2.8% of cases revealed methylation of more than one gene. Based on their World Health Organization 2007 grade; 6.3% of grade I cases, 35.3% of grade II cases, and 33.3% of grade III cases showed hypermethylation in the promoter regions of the genes studied. No statistically significant relation was found between promoter zone methylation and factors such as age, sex, histopathology, grade, or recurrence., Conclusions: Further research on promoter zone methylation will help expose the methylation profile and pathogenesis of meningiomas, which will consequently guide to a deeper understanding of the pathogenesis of the disease, thus ensuring a better understanding of the prognosis and considering novel treatment options.

With the availability of molecular monitoring of BCR-ABL1 and the use of tyrosine kinase inhibitors, treatment in chronic myeloid leukemia (CML) is now molecularly focused. Eighty-three samples taken at different time points from 38 CML patients; were subjected to T315I mutation analysis and gene expression analysis of AHI1; a novel gene that is thought to have a role in both BCR-ABL1 mediated leukemic transformation and response to tyrosine kinase inhibitors. Only one patient (2.63%) harboured the T315I mutation. While no significant difference in AHI1 expression was observed between newly diagnosed CML samples and non-CML controls; CML samples under imatinib therapy had levels significantly higher than both newly diagnosed samples and controls. In the first 6 months of imatinib therapy, AHI1 expression was found to increase and then gradually decrease. There was no significant difference between imatinib responders and non-responders, while dasatinib caused significantly lower AHI1 levels. It is proposed that the change in AHI1 expression during CML therapy might be under the control of mechanisms independent from BCR-ABL1. AHI1 mediated signalling could be better understood by analyzing AHI1 gene expression levels in a greater number of patients and concurrently investigating JAK/STAT and Src family kinases pathways.

Recent studies have demonstrated that vegetable rich diets have protective effects on the occurrence and prognosis of various cancers. In addition to dietary intakes, ascorbic acid and β-carotene are also taken as supplements. The aim of this study was to assess effects of ascorbic acid, β-carotene and their combinations on human hepatocellular carcinoma cell line HepG2. Ascorbic acid and β-carotene were applied to cells as plasma peak concentrations (70 and 8 μM, respectively) and their half concentrations (35 and 4 μM, respectively) for 24 and 48 h. Genotoxic and cytotoxic effects of ascorbic acid and β-carotene were evaluated by alkali single cell gel electrophoresis (SCGE), acridine orange/ethidium bromide staining patterns of cells (apoptosis and necrosis) and lipid peroxidation (thiobarbituric acid reactive substances, TBARS). Results of the SCGE demonstrated that both ascorbic acid and β-carotene caused DNA damage on HepG2 which were also concordant to increased apoptosis and necrosis of cells. Increased TBARS values also demonstrated increased lipid peroxidation in these cells. Results of the present study demonstrates that when dietary intakes of ascorbic acid and β-carotene and their relevant achievable plasma level concentrations were considered, both ascorbic acid and β-carotene induce genotoxic and cytotoxic damage on HepG2 together with increased oxidative damage in contrast to their protective effect on healthy cells. This may be correlated to oxidative status and balance of ROS in hepatocellular carcinoma cells.

Adequate copper (Cu(2+)) concentrations are required for plants; however, at higher concentrations it can also cause multiple toxic effects. In the present study, lipid peroxidation, hydrogen peroxide levels as well as ascorbate peroxidase (APX: EC 1/11/1/11) and catalase (CAT: EC 1.11.1.6) activities were determined in Lycopersicum esculentum Mill. and Cucumis sativus L. seedlings after 7-day exposure to copper sulfate. In addition, DNA damage in these two crops was assessed by measuring micronucleus (MN) frequency and tail moments (TM) as determined by Comet assay. Inhibitory copper concentrations (EC(50): 30 and 5.5 ppm for L. esculentum and C. sativus, respectively) were determined according to dose-dependent root inhibition curves, and EC(50) and 2×EC(50) were applied. Malondialdehyde (MDA) and H(2)O(2) levels significantly increased in all groups studied. CAT activity increased in treatment groups of C. sativus. APX activity increased in L. esculentum seedlings due to 2×EC(50) treatment. Reductions in mitotic indices (MI) represented Cu(2+)dependent root growth inhibition in all treatment groups studied. According to TMs and MN frequencies, copper exposure induced significant DNA damage (p < 0.05) in all study groups, whereas the DNA damage induced was dose dependent in C. sativus roots. In conclusion, Cu(2+)induced oxidative damage, elevations in H(2)O(2) levels and alterations in APX and CAT activities, as well as significant DNA damage in nuclei of both study groups. To our knowledge, this is the first comparative and comprehensive study demonstrating the effects of copper on two different plant species at relevant cytotoxic concentrations at both biochemical and genotoxicity levels with multiple end points.

The amount or quality of available septal cartilage may be inadequate for grafting in some rhinoplasty patients. In such cases, auricular or costal cartilage may provide an additional source of cartilage. Crushed septal cartilage has been shown to be useful for dorsal onlay grafts. We aimed to investigate the effect of different degrees of crushing on the viability of human auricular and costal cartilage. Ten auricular and 10 costal cartilage grafts were obtained from 20 patients during secondary rhinoplasty. Each graft was sectioned into five pieces. One of the pieces was left intact and the remaining four were prepared as slightly, moderately, significantly, and severely crushed. Viability and proliferation rates of chondrocytes in cell cultures were evaluated. Mean viability rates on day 1 for intact, slightly crushed, moderately crushed, significantly crushed, and severely crushed auricular cartilages were 70%, 67%, 65%, 58%, and 45%; while those for costal cartilages were 65%, 63%, 59%, 55%, and 53%, respectively. There was no statistically significant difference between the viability rates of the similarly crushed auricular and costal cartilage groups on days 1, 2, 3 and 10. The viability of crushed human auricular and costal cartilage grafts depends on the degree of crushing applied., (Copyright © 2010 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Objective: To determine the efficacy of the preimplantation cytogenetic analysis of the embryos obtained from patient with mosaic Turner syndrome before an IVF program., Design: Prospective cytogenetic analysis., Setting: University-based tertiary medical center., Patient(s): A 29 year-old female, a partner in a couple with male factor infertility, was diagnosed with mosaic Turner syndrome with a 45,X [17]/46,XX [13] karyotype., Intervention(s): Preimplantation genetic diagnosis was performed on four blastomeres obtained from four different embryos by fluorescence in situ hybridization probes specific to chromosomes X, Y, 13, 18, 21 in an intracytoplasmic sperm injection cycle., Main Outcome Measure(s): Blastomeres with normal signals., Result(s): Two blastomeres detected as normal were transferred and pregnancy was achieved., Conclusion(s): Preimplantation Genetic Diagnose should be considered in the infertility treatment of the patient with mosaic Turner Syndrome., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Amplification and/or overexpression of HER-2/neu has been reported to be associated with poor prognosis in breast cancer. One single-nucleotide polymorphism at codon 655 indicates a guanine-to-adenine substitution (Ile655Val) in the transmembrane domain-coding region of the HER-2/neu gene reported to be associated with increased risk of breast cancer. However, several studies have shown that this association is controversial. In this study, we aimed to evaluate the association between HER-2 codon 655 polymorphisms and breast cancer risk in breast cancer patients. We analyzed the HER-2 codon 655 polymorphisms in paraffin block sections from 58 breast cancer patients and 55 control subjects and evaluated the association of the polymorphic alleles with breast cancer. Following DNA isolation, polymerase chain reaction-restriction fragment length polymorphism analysis was carried out. The polymorphic Val allele was detected in 12.1% of the patients and in 17.3% of the control subjects. When the results of the study were evaluated, no statistically significant correlation was found between HER-2/neu codon 655 polymorphism and breast cancer.

Multiple myeloma (MM) is a B-cell neoplasia characterized by the clonal proliferation of plasma cells. Besides known genetic abnormalities, epigenetic changes are also known to effect MM pathogenesis. DNA methylation is an epigenetic mechanism that silences genes by adding methyl groups to cytosine-guanine dinucleotides at the promoter regions. In this study, the methylation status of four genes; p16, O6-methyl guanine DNA methyl transferase (MGMT), death-associated protein kinase (DAPK) and E-cadherin (ECAD); at the time of diagnosis was investigated using methylation-specific polymerase chain reaction (MS-PCR). In the 20 cases studied; methylation of the promoter regions of p16, MGMT, DAPK and ECAD genes was detected in 10%, 40%, 10% and 45% of the cases, respectively. In 65% (13/20) of cases, at least one of the genes studied had promoter methylation; while 35% of cases (7/20) had methylated promoters of more than one gene. There was a significant correlation between promoter hypermethylation of MGMT and the presence of extramedullary involvement; but for the other genes no correlation was found regarding disease properties like age, disease stage, clinical course and the presence of lytic bone lesions. Determining the methylation profiles of genes in MM, could lead to a new understanding of the disease pathogenesis and guide the assessment of treatment options.

Partial trisomy syndrome of chromosome 9 is one of the frequent autosomal trisomies with a well defined phenotype. Here we report two cases with different karyotypes and we aim to compare the phenotypic findings. The first case was an 8.5 months old boy with developmental delay. He had mental and motor retardation, microcephaly, bilateral undescended testes and multiple minor malformations. The karyotype was 46,XY,-7,der(7)t(7;9)(q36;p12) pat. The second case was a 5 year old boy with mental and motor retardation. He had atypical facial appearance with bilateral undescended testes. The karyotype was reported as 47,XY,+del(9)(q22.1 qter)dn[46]/ 46,XY[4]. Partial trisomy 9 syndrome has a wide range of clinical findings depending on the size of the trisomic chromosome segment. Newly diagnosed cases and their chromosome findings will add to the understanding of the syndrome.

Background: Expression of matrix metalloproteinase (MMP)-9 increases in nasal polyp tissues. However, the impact of MMP-9 genotypes on the development of nasal polyposis (NP) is unknown. The aim of this study was to examine a potential association of MMP-9 promoter gene polymorphism with the development of NP., Methods: A prospective and case-control study was performed on 93 patients with NP and 115 controls without sinonasal disease. Genotypes of MMP-9 (-1562C>T) were identified by restriction fragment length polymorphism analyses after polymerase chain reaction., Results: The frequency of -1562CT genotype of MMP-9 was significantly high in NP patients with aspirin-induced asthma (p = 0.014). Distribution of T allele was significantly high in NP patients with aspirin-induced asthma (p = 0.013). MMP-9 genotypes were not associated with gender or the presence of atopy., Conclusion: In this study, MMP-9 -1562CT genotype was associated with susceptibility to NP in aspirin-induced asthmatic patients. Because this report is a population-based study, further research should be performed on larger study subjects to reveal the precise role of MMP-9 promoter gene polymorphism in the development of NP.

The authors report a 5.5-year-old male patient with a right paraspinal tumor, diagnosed as metastatic Ewing sarcoma. The pleural fluid along with the bone marrow was sent to the authors' laboratory for karyotyping. Bone marrow cultures revealed a normal karyotype, whereas 48, XY, i(1)(q11), +10, t(11;22)(q24;q12) karyotype was found in the cells obtained from the pleural fluid cultures. Trisomy 1q is quite frequently observed in Ewing sarcoma patients, mostly as part of unbalanced translocations, along with the common t(11;22) translocation. This patient's findings were significant, as the complex karyotype in the pleural effusion cells was observed.

Conventional cytogenetic analysis and fluorescence in situ hybridization (FISH) results of bone marrow samples of 36 multiple myeloma (MM) patients at the time of diagnosis have been evaluated. Three probes for chromosome 13q (RB1, D13S319, D13S25), one for 14q32 (IgH) and one for 17p13 (p53) have been used for hybridization with fixed cells. Twenty patients (55.5%) had normal karyotypes, whereas eight (22.2%) had numerical or structural chromosomal abnormalities. We did not find metaphases for chromosome analysis in eight (22.2%) patients. Fluorescence in situ hybridization analyses revealed at least one or more abnormal results in 25 (69.5%) cases, whereas 11(30.5%) cases had no abnormal findings. 14q32 rearrangement was the most common finding in FISH analyses and has been detected in 21 cases (58.3%). 13q deletion and 17p deletion have been detected in 11 (30.5%) and 5 (13.9%) cases, respectively. Fluorescence in situ hybridization studies including 14q32 and 17p13 chromosome regions may yield quite significant results during clinical follow-up of MM.

Aim: Meningiomas arise from the meningoendothelial cells and are one of the most common tumors of the central nervous system. The HER-2/neu gene is located on the 17q11.2-q12 chromosome region and encodes an epidermal growth factor receptor. HER- 2/neu gene amplification and/or over expression have been studied most widely in breast carcinomas. Previous studies have shown the importance of HER-2/neu gene amplification on the prognosis of meningioma cases. In this study, we aimed to detect HER-2/neu gene copy number in archive materials of 55 meningioma patients by fluorescent in situ hybridization (FISH)., Material and Methods: The patients included in the study had undergone surgery in the neurosurgery department of our hospital between 1999 and 2002. Tissue samples were classified histologically according to WHO 2007 guidelines. Interphase FISH was performed on 3 to 4microm thick paraffin embedded tissue sections for the detection of HER- 2/neu gene amplification status., Results: We found HER-2/neu gene amplification in 7 (12.73%) patients. Another 2 patients had only one signal for the HER-2/neu region. We confirmed this finding by a second hybridization with the chromosome 17p13.1 (p53) probe., Conclusion: According to our results, HER-2/neu amplification could be regarded as an additional genetic factor playing role in meningioma pathogenesis together with known chromosomal abnormalities.

Inflammatory bowel disease (IBD) with ulcerative colitis (UC) and Crohn's disease (CD) as the most common forms is an inflammation of the gastrointestinal tract. Familial Mediterranean fever (FMF) is another inflammatory disease as well. In the current study we studied FMF gene mutations in 47 patients with IBD and 25 healthy individuals to investigate the effects of these mutations on the clinical status of IBD. Twelve mutations were analyzed by reverse hybridization after multiplex PCR amplification of DNA samples. We did not find an association between FMF gene mutations and IBD phenotypic characteristics. However, in patients without Mediterranean fever (MEFV) mutations, extraintestinal disease frequencies were higher (p<0.05). IBD has a genetic basis with multiple genes probably playing a role via several pathways during disease progression. Studying other genes interacting with FMF gene in a larger group of patients will add to the knowledge of disease pathogenesis.