Association of CUL4B with the pathogenesis of age-related cataract.

PURPOSE: Age-related cataract (ARC) is the most common cause of visual impairment and blindness in older adults. However, the role of CUL4B in the ARC remains unclear. Therefore, we investigated CUL4B expression and its effects on apoptosis. MATERIALS AND METHODS: CUL4B expression levels were detected by a quantitative real-time polymerase chain reaction from the anterior lens capsules of patients with ARC and HLE-B3 cells treated with different concentrations of H2O2. CUL4B expression was silenced by siRNA transfection to evaluate apoptosis. CUL4B and apoptotic proteins B cell lymphoma 2 (Bcl-2), myeloid cell leukemia 1 (Mcl-1), caspase-3, cleaved caspase-3, Bax, Bak, and Bid were assessed using western blot analysis. Apoptosis was monitored using the TUNEL assay. RESULTS: CUL4B expression was downregulated in the anterior lens capsules (P < 0.0001) and H2O2-treated HLE-B3 cells (P = 0.0405). CUL4B protein levels were significantly lower in 100 µmol/L (P = 0.0012) and 200 µmol/L (P = 0.0041) H2O2-treated HLE-B3 cells than in the untreated cells. CUL4B expression was significantly knocked down at the mRNA (P = 0.0043) and protein levels (P = 0.0002) in HLE-B3 cells. Bcl-2 (P = 0.0199), Mcl-1 (P = 0.0042), and caspase-3 (P = 0.0142) were significantly downregulated, whereas cleaved caspase-3 (P = 0.0089) and Bak (P = 0.009) were significantly upregulated in the knockdown group. The TUNEL assay showed a greater induction of apoptosis. CONCLUSIONS: CUL4B downregulation promotes the apoptosis of lens epithelial cells. Our study may help in understanding the role of CUL4B in ARC pathogenesis.

Evaluation of Clinical and Laboratory Factors Affecting Bone Mineral Density Measurements in Patients with Kidney Transplant.

Histological evidence of osteodystrophy and osteopenia is encountered in most patients who have undergone successful renal transplantation. Renal transplantation may be beneficial for correcting uremia-related problems in end-stage renal disease patients; however, its benefit is limited in bone metabolism disorders. The present study aims to evaluate bone mass measurements and investigate the influencing factors in patients with renal transplant. One hundred and eighteen patients (83 males and 35 females) with a mean age of 40.2 ± 11.8 yr (range 20-67) were included in the present study. The laboratory and the clinical data of the patients were retrospectively analyzed. The association between bone mineral density (BMD) measurements and the demographic characteristics of the patients, serum creatinine, parathormone, calcium, phosphorous, alkaline phosphatase, 25-hydroxyvitamin D and the glomerular filtration rate were evaluated. Of the patients, 23.7% (n =28) had normal, 48.3% (n = 57) had osteopenic and 28% (n = 33) had osteoporotic BMD values. A significant positive correlation was determined between the body mass index (BMI) and the BMD measurement results (p = 0.001; r = 0.385). A negative correlation was determined between the BMD values and the serum parathormone (p = 0.012; r = -0.237). BMD values were significantly lower in the group that had not received mammalian target of rapamycin (mTOR) inhibitor (p = 0.026). Conclusion: BMI values, mTOR inhibitor treatment and serum parathormone levels had an effect on the BMD measurement values.

Clinical and molecular evaluation of MEFV gene variants in the Turkish population: a study by the National Genetics Consortium.

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.

Evaluation of coagulation parameters in patients with parathyroid adenoma.

Parathyroid adenoma is responsible for 80-85% of cases of primary hyperparathyroidism. Increased fibrinogen levels in patients with adenoma may increase the risk of atherosclerosis and cardiovascular events. The aim of this study was to investigate the relationship between coagulation parameters and parathyroid adenoma. A prospective study included 28 female patients with parathyroid adenoma aged 40-88 years and 27 age-matched healthy controls. The coagulation parameters were assessed for each participant. The mean ages of the patient and control groups were 57.7 ± 10.9 and 53.3 ± 9.31 years, respectively. The mean level of protein S activity was 65.79 ± 13.78 in the patient group and 77.00 ± 15.72 in the control group, and the difference was statistically significant (p = 0.013). The mean fibrinogen levels of the patient and control groups were 338.78 ± 63.87 mg/dL and 304.30 ± 45.67 mg/dL, respectively, and a significant difference was found (p = 0.041). However, no significant difference was evident between the two groups with regard to the D-dimer (p = 0.238), aPTT (p = 0.645), INR (p = 0.406), protein C (p = 0.076), and AT-III (p = 0.180) levels. A positive correlation was observed between adenoma volume and fibrinogen in the patient group (r = 0.711, p = 0.001). The protein S levels were lower and the fibrinogen levels higher in the patients with parathyroid adenoma.

Proteomic analysis of the anticancer effect of various extracts of endemicThermopsisturcica in human cervical cancer cells

Background/aim: Thermopsisturcica is a perennial species endemic to Turkey and different extracts of T. turcica have an antiproliferative effect on cancer cells, but there has not been any report on HeLa (human cervical cancer) cells. Materials and methods: To get a better understanding of the molecular mechanism of anticancer activity of methanolic extracts of leaves (LE) and flowers (FE) of T. turcica, we employed 2-DE-based proteomics to explore the proteins involved in anticancer activity in HeLa cells. Results: T. turcica extracts showed a potent cytotoxic effect on HeLa cells with the IC50 values of 1.75 mg/mL for LE and 3.25 mg/mL for FE. The induction of apoptosis by LE and FE was also consistent with increased expression of caspase mRNAs and DNA fragmentation. In terms of the proteomic approach, 27 differentially expressed proteins were detected and identified through MALDI-TOF/TOF mass spectrometry. These altered proteins were involved in cytoskeleton organization and movement, protein folding, proteolysis and translation, cell cycle and proliferation, signal transduction, cell redox homeostasis, and metabolism. Conclusion: Up-regulation of protein disulfide isomerases and down-regulation of Rho GDP-dissociation inhibitor, heterogeneous nuclear ribonucleoproteins, and heat shock proteins may contribute to the induction of apoptosis and arresting of the cell cycle in HeLa cells.

Effect of Insulin Therapy on Ocular Biometric Parameters in Diabetic Patients.

Purpose: To evaluate effects of insulin on ocular parameters in patients with type 2 diabetes mellitus who start insulin therapy. Methods: In this prospective study, ocular biometric parameters were obtained using optical biometer (Lenstar LS900®; Haag-Streit AG) and refraction test (ARK-510A Auto refracto-keratometer; Nidek Co. Ltd, Aichi, Japan) before and at 3 months after initiating insulin therapy. In addition, patients' fasting blood glucose (FBG), glycosylated hemoglobin (HbA1C), and blood lipid levels were measured at the same time points. Pretreatment and post-treatment results were compared. In addition, associations between ocular parameters with initial dose and type of insulin treatment regimen, HbA1C, and FBG levels were evaluated. Results: The patients' mean age was 51.2 ± 12.9 (18-73) years. Post-treatment HbA1C and FBG levels (8.5% ± 2.5% and 188.1 ± 111.2 mg/dL, respectively) were significantly lower than pretreatment values (12% ± 1.4% and 325.3 ± 95.7 mg/dL, respectively; P < 0.001 for both). There was a significant positive correlation between the change in HbA1C and the change in lens thickness (P = 0.03), and a significant negative correlation between the change in FBG and the change in the spherical equivalent refraction (P = 0.045). Insulin dose and treatment regimen type were not significantly correlated with ocular parameters (P > 0.05). Conclusion: HbA1C-lowering glycemic effect of insulin was correlated with a small decrease in lens thickness. Long-term, randomized controlled trials including larger patient numbers are needed to shed light on the long-term effects of insulin use and glycemic control on ocular parameters.

A comparison of haemogram parameters of patients with thyroid papillary cancer and nodular goiter in Van, Turkey.

OBJECTIVE: To compare the haemogram parameters of patients with thyroid papillary cancer and nodular goiter. METHODS: The retrospective comparative study was conducted at Van Training and Research Regional Hospital, Van, Turkey, and comprised data of patients who underwent thyroidectomy from 2011 to 2015. The data was compared between patients with papillary thyroid cancer (group 1) and those with nodular hyperplasia (group 2) in terms of age, gender and thyroid stimulating hormone level as well as haemogram parameters, neutrophil-lymphocyte ratio and platelet-lymphocyte ratio. SPSS 20 was used for statistical analysis. RESULTS: Of the 90 patients, 53(59%) were in group 1 with papillary thyroid cancer and 37(%) in group 2 with nodular hyperplasia. Platelet-lymphocyte ratio was significantly higher in group 1 (p=0.015). Mean platelet volume was significantly higher in group 1 patients with a diameter of 1cm or more (p<0.05). Within group 1, lymphocyte count was significantly high in patients with invasion (p<0.05). In correlation analysis, group 1 patients with a tumour diameter of 1cm or more showed a significant correlation in mean platelet volume, tumour multicentricity, lymphocyte count, vascular invasion, thyroglobulin, platelet distribution width, platelet number and tumour multicentricity (p<0.05). CONCLUSION: Only platelet-lymphocyte ratio could assist in distinguishing benign goiter from thyroid cancer. Also, mean platelet volume, lymphocyte count, and platelet distribution width appeared to be effective prognostic markers for papillary thyroid cancer.

Decreased bone mineral density and associated factors in severe haemophilia A patients: A case-control study.

INTRODUCTION: Haemophilia patients may exhibit lower levels of bone mineral density (BMD) than the general population for a variety of reasons. AIM: We aimed to investigate decreased BMD in people with severe adult haemophilia A (PWH) living in eastern Turkey, and to evaluate the related potential risk factors. METHODS: The study included 41 PWH and 40 healthy volunteers. Dual-energy x-ray absorptiometry (DXA) was used to measure the BMD. Blood tests and body mass index (BMI) were recorded. The Functional Independence Score in Hemophilia (FISH) test was used to measure functional ability status. RESULTS: There was a significant difference between the PWH and control groups with respect to femoral neck and total hip BMD (in g/cm2 ), but the difference for lumbar spine was not significant (P = .017, P < .001, P = .071, respectively). In PWH, patients under 50 years of age, 19.4% were found to have "lower than expected" BMD levels for their age, while 27.8% showed "low normal" levels. In PWH, osteoporosis was found in 60% of the patients over 50 and osteopenia in 20%. Vitamin D insufficiency and deficiency were present in 63.4% of the PWH, significantly higher than the control group (37.5%; P < .001). CONCLUSION: The results indicated that the decrease in BMD was significantly greater in patients with severe haemophilia A than in the normal healthy population. This reduction was correlated with BMI, vitamin D and low functional ability status. However, in multivariate analysis, none of these was a strong independent risk factor.

Relationship between SIRT1 gene expression level and disease in age-related cataract cases

Background/aim: Age-related cataract is the most important visual impairment all over the world. Epigenetic modifications, especially overexpression of histone deacetylases, have become the focus of interest for cataract development in recent years. Sirtuin 1 (SIRT1), a class II histone deacetylase and a member of the sirtuin family, is one of the best-characterized histone deacetylases and has a pivotal role in age-related diseases. However, the association of SIRT1 with age-related cataracts has not yet been fully elucidated. Therefore, we aimed to determine the expression of SIRT1 in age-related cataract patients. Materials and methods: Expressions of SIRT1 were evaluated by quantitative polymerase chain reaction (qPCR) in patients and healthy controls. RNA samples were collected from the anterior capsule and peripheral blood samples of age-related cataract patients. Human lens epithelial cell line B3 and peripheral blood samples of healthy subjects were used as controls. Results: We determined that the expression of SIRT1 in blood and anterior capsule samples increased significantly compared to the control group (P < 0.05). Conclusion: The expression level of SIRT1 plays a vital role in the development of age-related cataract and it can be used as a biomarker. Thus, SIRT1 inhibitors can be used in the treatment of age-related cataract disease.

The relationship between atypical depression and insülin resistance in patients with polycystic ovary syndrome and major depression.

In this study, we aimed to examine the relationship between atypical depression and insulin resistance (IR) in patients with polycystic ovary syndrome (PCOS) and major depression. A total of 176 subjects (69 patients with PCOS, 58 patients with depression, and 49 healthy controls) were included in the study. The Beck Depression Inventory (BDI), the Beck Anxiety Inventory (BAI), the Beck Hopelessness Scale (BHS), and the Scale for Suicide Ideation (SSI) were administered. Data concerning their height, weight, fasting a.m. serum levels of insulin, glucose level, and total testosterone level were collected from all participants. The body mass index (BMI) and the Homeostasis Model Assessment Insulin Resistance index (HOMA-IR) were both calculated. 34 (49.3%) of the PCOS patients met the criteria for depression. 26 (76.5%) of them had atypical depression, 8 (23.5%) had non-atypical depression. 27 (46.6%) of the 58 depressed patients had atypical depression. Insulin resistance was higher in the PCOS patients than in the control subjects and the depression patients. There was no association between atypical depression and IR in patients with PCOS and depression. We concluded that there is no relationship between IR and atypical depression.

Assessment of Pain Sensitivity in Patients With Chronic Low Back Pain and Association With HTR2A Gene Polymorphism.

OBJECTIVES: This study aims to investigate the association of two common HTR2A gene polymorphisms, rs6313 (102 T/C) and rs6311 (1438 A/G), with chronic low back pain (CLBP) and the pain threshold, disability, and sex differences. PATIENTS AND METHODS: A total of 121 patients (40 males, 81 females; mean age 36.8±9.9 years; range 18 to 50 years) having CLBP and 91 healthy controls (26 males, 65 females; mean age 34.1±10.2 years; range 18 to 55 years) were included. Pressure pain thresholds (PPTs) of all participants were examined with manual algometer in certain sites of their body. RESULTS: The PPTs were all decreased in CLBP patients (p<0.05). Although PPTs were lower in healthy female subjects, there was no sex difference regarding PPTs in CLBP patients (p>0.05). rs6311 polymorphism of HTR2A gene was associated with CLBP (p<0.05). In rs6313 polymorphism, at least one copy of T carriers and in rs6311 polymorphism, at least one copy of G carriers showed higher disability. CONCLUSION: The PPT decreases in CLBP patients similar to other chronic pain conditions without any sex difference. Although rs6311 single nucleotide polymorphism of HTR2A gene was associated with CLBP and rs6313 polymorphism was not, rs6311 might have a protective effect on disability of these patients.

Association of rs11209032 and rs1004819 Polymorphisms in Interleukin-23 Receptor Gene With Ankylosing Spondylitis.

OBJECTIVES: This study aims to investigate the distribution of human leukocyte antigen B27 (HLA-B27) alleles (+/-) and interleukin-23 receptor (IL-23R) gene rs11209032 and rs1004819 polymorphisms among ankylosing spondylitis (AS) patients in a Turkish cohort. PATIENTS AND METHODS: The study sample comprised 106 AS patients (89 males, 18 females; mean age 38.9±10 years; range 19 to 65 years) and 82 healthy controls (70 males, 12 females; mean age 32.15±7.07 years; range 19 to 51 years). Distribution of HLA-B27 alleles (+)/(-) in AS patients were observed by reverse hybridization technique. Genotyping of IL-23R rs11209032 and rs1004819 polymorphisms of AS patients and healthy controls were performed by real time polymerase chain reaction. RESULTS: Of the AS patients, 69 (65.1%) were HLA-B27 positive. Distribution of rs11209032 genotype frequencies in AS group were 31.1% for GG, 50.9% for GA, and 17.9% for AA; while in control group, it was 34.1% for GG, 53.7% for GA, and 12.2% for AA. Distribution of rs1004819 genotype frequencies in AS group were 30.2% for CC, 52.8% for CT, and 17.0% for TT; while in control group, it was 42.7% for CC, 46.3% for CT, and 11.0% for TT. There was no significant difference between AS patients and controls in terms of genotype frequencies of IL-23R gene rs11209032 and rs1004819 polymorphisms. CONCLUSION: No association was found between AS and IL23R rs11209032 and rs1004819 polymorphisms in this Turkish AS cohort.

Association of Alzheimer's Disease With APOE and IL-1α Gene Polymorphisms.

Apolipoprotein E (ApoE) gene polymorphisms are thought to be the most important genetic risk factor in the pathogenesis of late onset and sporadic Alzheimer's disease (AD). Moreover, interleukin-1α (IL-1α) is found to be associated with the pathogenesis of AD. In this research, ∊2, ∊3, and ∊4 polymorphisms of ApoE gene and C889T polymorphism of IL-1α gene were genotyped in patients with AD and controls. Genotyping was performed by real-time polymerase chain reaction. ∊3/∊3 and ∊3/∊4 genotype frequencies were significantly higher in control and case groups, respectively. While ∊3 allele frequencies were significantly higher in the control group, ∊2 and ∊4 allele frequencies were significantly higher among the cases with AD. No difference was found between the groups according to C889T polymorphism of IL-1α. In conclusion, we demonstrated that there was a strong association between ApoE ∊4 allele and AD, while there was no relation with IL-1α C889T polymorphisms for this study.

Association of obesity with rs1421085 and rs9939609 polymorphisms of FTO gene.

The aim of this study is to investigate the genetic influence of polymorphisms in fat mass and obesity associated (FTO) gene on a sample of obese subjects and controls. Obesity is an epidemic all over the world. Several polymorphisms in the first intron of FTO gene have been associated with common forms of human obesity. In this research rs1421085 and rs9939609 polymorphisms of FTO gene were genotyped in 190 obese patients with a BMI ≥30 kg/m(2) (Body Mass Index) and 97 healthy controls with a BMI of 18.5-24.9. Genotyping of SNPs was performed by real-time polymerase chain reaction. Body composition was established with bioelectric impedance analysis. Waist-to-hip ratio was determined for all participants. There were no significant differences (P > 0.05) between obese cases and controls in terms of genotype frequencies of rs1421085 and rs9939609 polymorphisms in our study. Also there were no significant correlations between genotypes and obesity related (anthropometric-body composition) parameters (P > 0.05).

Coexistence of chronic renal failure, hashimoto thyroiditis and idiopathic hypoparathyroidism: a rare case report.

Hypoparathyroidism is an uncommon disease and its coexistence with chronic renal failure is quite rare. Hypocalcemia and hyperphosphatemia are seen in both diseases. Diagnosis of hypoparathyroidism may be overlooked when parathormone response is not evaluated in patients with chronic renal failure. A 19-year-old female patient who had been receiving hemodialysis for 3 years because of chronic renal failure was diagnosed as idiopathic hypoparathyroidism and hashimoto thyroiditis. When her medical records on the first admission and medical history were evaluated, hypoparathyroidism and hashimoto thyroiditis were seen to be present also when she was started hemodialysis. Idiopathic hypoparathyroidism should be suspected in case as absence of parathormone response to hypocalcemia in patients with chronic renal failure. It should be taken into consideration that hashimoto thyroiditis may accompany and required analysis should be done.

Association of schizophrenia with T102C (rs6313) and 1438 A/G (rs6311) polymorphisms of HTR2A gene.

OBJECTIVE: The aim of this study is to investigate whether there were any associations between the T102C and 1438 A/G polymorphisms of the 5-HT2A receptor gene and schizophrenia. We conducted a case-control study of the T102C and 1438 A/G polymorphisms in Turkish patients. METHODS: We compared genotypes and allele frequencies of T102C and 1438 A/G polymorphisms of 5-HT2A receptor gene in 102 patients with schizophrenia diagnosed, according to DSM-IV, and 107 healthy controls. Genotyping was performed by real-time polymerase chain reaction. RESULTS: We found no significant association between schizophrenia and genotypic or allele frequencies of HTR2A gene 102T/C (rs6313) and 1438 A/G (6311) polymorphisms. However, comparison of HTR2A gene 102 T/C and 1438 A/G polymorphisms in terms of genotypic and allele frequencies between the two patient groups, with or without a family history of schizophrenia, shows that T- and A-allele frequencies were significantly higher (p < 0.05) in the case group that has a history of schizophrenia in their family. CONCLUSION: In conclusion, our results do not support the hypothesis that the T102C and 1438 A/G polymorphisms in the 5-HT2A receptor gene are associated with schizophrenia, but further studies in a larger sample are needed.