Effect Of G2706A and G1051A polymorphisms of the ABCA1 gene on the lipid, oxidative stress and homocystein levels in Turkish patients with polycystıc ovary syndrome

<p>Abstract</p> <p>Background</p> <p>Obesity, insulin resistance and hyperandrogenism, crucial parameters of Polycystic ovary syndrome (PCOS) play significant pathophysiological roles in lipidemic aberrations associated within the syndrome. Parts of the metabolic syndrome (low HDL and insulin resistance) appeared to facilitate the association between PCOS and coronary artery disease, independently of obesity. ABCA1 gene polymorphism may be altered this components in PCOS patients.</p> <p>In this study, we studied 98 PCOS patients and 93 healthy controls. All subjects underwent venous blood drawing for complete hormonal assays, lipid profile, glucose, insulin, malondialdehyde, nitric oxide, disulfide levels and ABCA genetic study.</p> <p>Results</p> <p>In PCOS group fasting glucose, DHEAS, 17-OHP, free testosterone, total-cholesterol, triglyceride, LDL-cholesterol and fibrinogen were significantly different compare to controls. The genotype ABCA G2706A distribution differed between the control group (GG 60.7%, GA 32.1%, AA 7.1%) and the PCOS patients (GG 8.7%, GA 8.7%, AA 76.8%). The frequency of the A allele (ABCAG2706A) was higher in PCOS patients than control group with 13,0% and 23,2%, respectively. In this study, the homocystein and insulin levels were significantly higher in PCOS patients with ABCA G1051A mutant genotype than those with heterozygote and wild genotypes.</p> <p>Conclusions</p> <p>We found higher percentage of AA genotype and A allele of ABCA G2706A in PCOS patients compare to controls. The fasting insulin and homocystein levels were significantly higher in PCOS patients with ABCA G1051A mutant genotype than those with heterozygote and wild genotypes.</p

Role of cardiac drugs and flavonoids on the IRE1-JNK pathway as revealed by re-ranked molecular docking scores, MM/PBSA and umbrella sampling

Duzgun, Zekeriya/0000-0001-6420-6292WOS:000596984400001PubMed: 33251987One of the important causes of cardiac dysfunction is the triggering of apoptosis through the IRE1-JNK signaling pathway due to excessive ER stress (endoplasmic reticulum stress). Although there are various studies on beneficial or harmful side effects of cardiac drugs, knowledge about the molecular mechanism of their interactions on this pathway is very limited. in this study, we investigated interactions of statins, ace inhibitors, antiarrhythmic drugs and flavonoids in IRE1, ASK1(apoptosis signal-regulating kinase 1) and JNK1 at an atomic level in comparison with their well-known inhibitors. The rank of scores obtained from four different docking algorithms (Autodock 4, Autodock Vina, iGEMDOCK and GOLD) were combined so that they could be compared with each other and evaluated together. According to combined results, the most potent compound for each compound group was selected for molecular dynamics simulations, MM/PBSA (molecular mechanics/Poisson-Boltzmann surface area) and umbrella sampling calculations. We observed that the statin group drugs had the best affinity by interacting with ASK1 and JNK1 by having a similar effect with their inhibitors, and atorvastatin and pitavastatin came to the fore. Norizalpinine from the flavonoid group had a strong binding interaction with IRE1, and amiodarone from the antiarrhythmic drug group had high binding affinities with IRE1, ASK1 and JNK1. Our study has shown that atorvastatin, pitavastatin, norizalpinine and amiodarone may have a role in preventing cardiac dysfunctions caused by ER stress and may shed light on further in vitro and in vivo research. Communicated by Ramaswamy H. Sarm

Role of mTOR in glioblastoma

WOS: 000366537500002PubMed ID: 26341051Mammalian target of rapamycin (mTOR), which is a member of the serine/threonine protein kinase family, is a protein complex that has a central role of cell growth and proliferation. mTOR emerges as a critical cell growth checkpoint on phosphoinositide 3-kinase (PI3K) signaling pathway. In this case mTOR has become an important therapeutic target for glioblastoma (GBM) that is one of the most deadly types of cancer. Various combination treatments including inhibition of mTOR may provide more significant results in the treatment of GBM. In addition to new mTOR targets, which may have a plant origin form, more potent mTOR inhibitors by utilizing the computational methodology may emerge as a hope for GBM therapy. In the future, a better understanding of the functional properties of mTORC2 with its potent effective inhibitors may help design more efficiently GBM treatment modalities. (C) 2015 Elsevier B.V. All rights reserved

Suppression of STAT3 by chemically modified siRNAs increases the chemotherapeutic sensitivity of parental and cisplatin-resistant non-small cell lung cancer cells

WOS: 000334153000021PubMed ID: 24659656Purpose: Increased activation of the JAK-STAT signaling pathway is frequently observed in several primary cancers as well as cancer cell lines. Thus, targeting JAK-STAT pathway components by different molecular-biologic approaches in the search for new anticancer therapies has become widespread and resulted in encouraging outcomes. In this study, the effects of chemically modified anti-STAT3 small interfering (si)RNAs on cell viability, proliferation and apoptosis of parental and cisplatin resistant non-small cell lung cancer (NSCLC) cells were investigated with the aim to provide a new therapeutic strategy for overcoming cisplatin resistance in lung cancer. Methods: The parental NSCLC cell line Calu1 and its cisplatin-resistant subline CR-Calu1 were used to study the effects of STAT3 suppression with chemically modified anti-STAT3 siRNAs. STAT3 gene and protein expressions were analyzed by real-time (RT) quantitative (q) PCR and Western blot, respectively. Apoptosis was evaluated by Caspase-3 activity and cell death assays. Results: STAT3 messenger (m)RNA and protein expression were significantly increased in CR-Calu1 cells and suppressing its expression with specific siRNAs increased the rate of apoptosis through Caspase-3 activation. STAT3 suppression also significantly increased cisplatin sensitivity of Calu1 and CR-Calu1 cells after transfection with STAT3 siRNAs. Conclusions: NSCLC cells could be sensitized to cisplatin by targeting STAT3 with chemically modified siRNAs together, a fact which was accompanied with increased apoptosis

The Relationship of the Peroxisome Proliferator Activated ReceptorGamma 2 Exon 2 and Exon 6 Gene Polymorphism in Type 2 Diabetic Patients with and without Diabetic Foot Ulcers

We aims investigate Turkish type 2 diabetic patients with/without diabetic foot ulcers and healthy group and examined the contribution of the G/C exon 2 and T/C exon 6 of the PPARgamma gene polymorphism to the development of diabetic foot ulcers. The PPARgamma genotypes were determined prospectively in 50 patients with diabetic foot ulcers and 50 without diabetic foot ulcers and a control group of 50 healthy individuals. Genotyping of the G/C exon 2 and T/C exon 6 of the PPAR-gamma gene polymorphism for all individuals was performed by melting curve analysis of the generated amplicons after real-time online PCR. The genotype exon 2 and exon 6 distribution did not differ between the control group and the type 2 diabetes mellitus patients (with and without diabetic foot) (P&gt;0.05). The frequency of the polymorphic G allele in exon 2 was no similar for the groups (6% and 1%, respectively) (p0.05). The evaluation of exon 2 and exon 6, genotype and haplotype did not show statistically significant difference between the patient diabetic foot and without diabetic foot (p&gt;0.05). The G/C exon 2 and T/C exon 6 of the PPARgamma gene polymorphism is not an independent risk factor for diabetic foot in Turkish type 2 diabetes mellitus patients. Genetic factors in the pathogenesis of diabetic foot may also show any changes in different populations. [Med-Science 2014; 3(4.000): 1582-94

Absence of apolipoprotein B-3500 mutation in Turkish patients with coronary and cerebrovascular atherosclerosis

WOS: 000254244400003PubMed ID: 18258526Objective: The arginine-to-glutamine change at codon 3500 of the apolipoprotein B-100 (apo B) is a well-known genetic cause of hypercholesterolemia. Since increased cholesterol levels lead to atherosclerosis, identification of the carries of the apo B-3500 mutation is an important step in the risk stratification of individuals and families with hypercholesterolemia. The prevalence of this mutation in Turkish population is not well known. We aimed to investigate the frequency of apo B-100 mutations (codon 3500) C9774T (Arg 3500 -> Trp) and G9775A (Arg 3500 -> Gln) in patients with atherosclerosis in comparison with healthy subjects. Methods: This cross-sectional study included 442 unrelated subjects living on the West coast of Turkey. Subgroups consisted of 165 patients with coronary artery disease, 163 patients with ischemic stroke, and 114 healthy control subjects. Results: We did not find any apo B-100 mutation both in the patient and control groups. Conclusion: As it is hypothesized that this mutation arose within the Central European region from a common ancestor approximately 7000 years ago and spread across Europe, our result of the absence of the R3500Q mutation in Turkish patients give an important information about the geographical distribution of the apo B-R3500Q, that the mutation has not reached to Anatolia