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

One 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.

Effect of SIRT1 activators and inhibitors on CD44+/CD133+‑enriched non‑small cell lung cancer cells.

Lung cancer is one of the most commonly diagnosed cancers and it is associated with high rates of morbidity and mortality. Metastasis and relapse of the tumor depend on the survival and proliferation of lung cancer stem cells (LCSCs). The ability to identify CSCs may prevent recurrence and lead to more effective treatments.

The relationship of the endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) gene polymorphism in Turkish type 2 diabetic patients with and without diabetic foot ulcers.

Objective: This study aims to evaluate the influence of eNOS G894T and VEGF C936T gene polymorphism in diabetic foot ulcers.

Method: We studied 50 patients with diabetic foot ulcers and 57 diabetic patients without diabetic foot ulcer and a control group of 75 healthy individuals.

Results: The genotype eNOS distribution did not differ between Type 2 Diabetic Patients group and Diabetic Foot Ulcer group (P>0.

Case-control study on PCSK9 R496W (rs374603772) and D374Y (rs137852912) mutations in Turkish patients with primary dyslipidemia.

Objective: The aim of this study was to investigate the relationships between F216L (rs28942112), R496W (rs374603772), S127R (rs28942111), and D374Y (rs137852912) PCSK9 gain-of-function (GOF) mutations and primary dyslipidemia and serum lipid levels in patients with primary dyslipidemia.

Methods: In this case-control study, DNA was isolated from blood samples collected from patients diagnosed with primary dyslipidemia in cardiology outpatient clinic of Ege University (n=200) and healthy individuals (n=201). F216L, R496W, S127R, and D374Y GOF mutations in the PCSK9 gene were evaluated and genotyped according to the results of melting curve analysis performed in a real-time polymerase chain reaction (PCR) 480 instrument using specific primers for each mutation.

Matrine induced G0/G1 arrest and apoptosis in human acute T-cell lymphoblastic leukemia (T-ALL) cells.

Matrine, a natural product extracted from the root of Sophora flavescens, is a promising alternative drug in different types of cancer. Here, we aimed to investigate the therapeutic effects and underlying molecular mechanisms of matrine on human acute lymphoblastic leukemia (ALL) cell line, CCRF-CEM. Cell viability and IC50 values were determined by WST-1 cell cytotoxicity assay.

PCSK 9 gain-of-function mutations (R496W and D374Y) and clinical cardiovascular characteristics in a cohort of Turkish patients with familial hypercholesterolemia.

Objective: The molecular basis of the mutations in the PCSK9 gene that produces familial hypercholesterolemia (FH) in the Turkish population is unknown. This study was conducted to determine the presence of four different PCSK9 gain-of-function (GOF) mutations (F216L, R496W, S127R, and D374Y) in a group of patients with FH.

Methods: A total of 80 consecutive patients with FH (mean age: 56±11 years; mean maximum LDL cholesterol: 251±76 mg/dL) were included in the study.

Polymorphisms of lipid metabolism enzyme-coding genes in patients with diabetic dyslipidemia.

Objective: The polymorphisms/mutations of genes encoding proteins and enzymes involved in lipoprotein metabolism play important roles in the development of diabetic dyslipidemia. The aim of our study was to investigate the effects of LPL (rs320), LIPC (rs2070895), SCARB1 (rs5888), LCAT (rs2292318), CETP (rs708272), ADIPOQ (rs1501299), RETN (rs3745367), PON1 (rs662), and MNSOD (rs4880) gene polymorphisms on lipid metabolism and diabetic dyslipidemia.

Methods: This case-control study included 217 patients with diabetic dyslipidemia and 212 healthy age- and gender-matched individuals.

LDLR C1725T Gene Polymorphism Frequency in Type 2 Diabetes Mellitus Patients With Dyslipidemia.

Background: Dyslipidemia has a substantial role in the development of cardiovascular diseases in patients with type 2 diabetes mellitus (T2DM). Determining the genetic profile of T2DM patients with dyslipidemia is important in order to reduce the risk of microvascular and macrovascular complications. Low-density lipoprotein receptor (LDLR) plays a critical role in plasma lipoprotein hemostasis.

Sequencing of mutations in the serine/threonine kinase domain of the bone morphogenetic protein receptor type 2 gene causing pulmonary arterial hypertension.

Objective: Germline mutations in the bone morphogenetic protein receptor type-2 (BMPR2) gene are considered to be a major risk factor for pulmonary arterial hypertension (PAH). BMPR2 mutations have been reported in 10%-20% of idiopathic PAH and in 80% of familial PAH cases. The aim of this study was to evaluate the frequency of mutations in the serine/threonine kinase domain of the BMPR2 gene in a group of patients from a single PAH referral center in Turkey.

The relationship of the apolipoprotein E gene polymorphism in Turkish Type 2 Diabetic Patients with and without diabetic foot ulcers.

Aims: The aim of this study was to investigate the association between Apolipoprotein E (ApoE) gene polymorphism in the development of diabetic foot ulcers in Type 2 diabetes Turkish patients.

Materials And Methods: The ApoE genotypes were determined retrospectively in 50 patients with diabetic foot and 50 without diabetic foot and a control group of 50 healthy individuals.

Results: The genotype ApoE distribution did differ between the control group (E2E3 44%, E3E3 38%, E3E4 18%) and Type 2 Diabetic Patients (E2E3 6%, E3E3 81%, E3E4 16%) (p<0.

Role of mTOR in glioblastoma.

Mammalian 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.

miR-15a enhances the anticancer effects of cisplatin in the resistant non-small cell lung cancer cells.

Platinum-based chemotherapies have long been used as a standard treatment in non-small cell lung cancer. However, cisplatin resistance is a major problem that restricts the use of cisplatin. Deregulated cell death mechanisms including apoptosis and autophagy could be responsible for the development of cisplatin resistance and miRNAs are the key regulators of these mechanisms.

An Association Study Between Gene Polymorphisms of Folic Acid Metabolism Enzymes and Biochemical and Hormonal Parameters in Acromegaly.

Aim: Folate metabolism is fundamental to several biological functions and required for cell replication, division, and survival. The mammalian folic acid cycle is highly complex and the enzymes, methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and methionine synthase reductase (MTRR), have crucial roles in this metabolic pathway. The common polymorphisms of the MTHFR (C677T and A1298C), MTRR (A66G), and MTR (A2756G) enzymes are well documented as folate deficiency-related disorders, but their roles have not been examined in acromegalic patients.

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

Purpose: 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.

Beta-myosin heavy-chain mutations R403QLW, V606M, K615N and R663H in patients with hypertrophic cardiomyopathy.

Objective: Hypertrophic cardiomyopathy (HCM) is a disease of the myocardium with an autosomal-dominant pattern of inheritance mainly caused by single heterozygous mutations in sarcomere genes. In this study we aimed to detect the presence of R403QLW, V606M, K615N, and R663H mutations in beta-myosin heavy-chain gene (MYH7) and figure out the genotype-phenotype correlations in Turkish patients with HCM.

Methods: This case-control study based on genotype-phenotype correlation included 69 patients (mean age, years: 50±13.

Identification of Y chromosome microdeletions in infertile Turkish men.

Objective: The aim of this study was to determine the frequencies of Y chromosome microdeletions in infertile azoospermic and oligozoospermic Turkish men and in healthy control subjects.

Material And Methods: Sixty-four azoospermic and 51 oligozoospermic patients infertile patients, and 70 healthy men who had a child without the aid of assisted reproductive technologies were included in this study. DNA was extracted from peripheral blood samples collected from the patients.

Is there any association between the Ser326Cys polymorphism of the 8-oxoguanine glycosylase 1 (OGG1) gene and risk of colon polyp and abnormal glucose tolerance in acromegaly patients?

Aim: Evidence arising from experimental studies indicates an association between increased levels of the growth hormone/insulin-like growth factor 1 and oxidative stress. The association of the Ser326Cys polymorphism in the 8-oxoguanine glycosylase (OGG1) gene with a colon carcinoma and diabetes mellitus has been examined. The aim of the study was to compare the genotypic distribution of OGG1 Ser326Cys between acromegaly patients and nonacromegalic subjects and to explore whether this polymorphism is associated with a colon polyp risk and abnormal glucose tolerance.

Role of 14-3-3σ in resistance to cisplatin in non-small cell lung cancer cells.

The efficacies of chemotherapeutic agents are often limited by side effects and acquired drug resistance. We have investigated whether the differential expression pattern of 14-3-3σ affects cisplatin response in non-small cell lung cancer cell lines. Two pairs of parental/cisplatin resistant cell lines (A549/CRA549 and Calu1/CR-Calu1) and clinical lung cancer biopsy samples were analysed for 14-3-3σ expression.

Acquired activated protein C resistance in sarcoma patients.

Acquired activated protein C resistance (aAPCR) is seen more frequently in solid and hematological cancer patients. We aimed to investigate the presence of aAPCR and the frequency of clinically detectable thrombosis in sarcoma patients. Normalized activated protein C sensitivity ratio (nAPCSR), factor V Leiden (FVL) mutation, factor V (FV) levels and factor VIII (FVIII) levels were prospectively measured in 52 patients and in 52 healthy controls.

Cisplatin resistance induced by decreased apoptotic activity in non-small-cell lung cancer cell lines.

We have investigated defective steps in apoptosis that might account for the development of resistance. For this purpose, A549 and Calu1 NSCLC (non-small-cell lung cancer) cell lines were treated with cisplatin to obtain resistant sub-lines. Gene expression profiles and the phosphorylation status of the BAD (Bcl-2/Bcl-XL-antagonist, causing cell death) protein were determined for each cell line.

Does Apolipoprotein E genotype affect cardiovascular risk in subjects with acromegaly?

Acromegaly is a syndrome that results when the pituitary gland produces excess growth hormone after epiphyseal closure at puberty. Usually, subjects with acromegaly exhibit a 2- to 3-fold higher mortality rate from diseases that are associated with cardiovascular complications when compared to the normal population. In this study, we therefore aimed to evaluate whether a well-established cardiovascular risk factor, the Apolipoprotein E (Apo E) genotype, contributes to increased risk of cardiovascular complications in subjects with acromegaly.

Factor V G1691A (Leiden) and prothrombiG20210A gene mutation status, and thrombosis in patients with chronic myeloproliferative disorders.

Objective: The aim of this study was to examine Factor V G1691A (Leiden) (FVL) and prothrombin G20210A (PT) gene mutation status, and their relationship with thrombosis in patients with chronic myeloproliferative disorders (CMPDs).

Methods: The study included 160 patients with a CMPD that were regularly followed-up between 1993 and 2009. FVL and PT mutation status was established based on blood samples analyzed via PCR using specific primers.

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.

Background: 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.

Methylenetetrahydrofolate reductase C677T gene polymorphism in Turkish patients with polycystic ovary syndrome.

Higher Levels of Hcy are associated with several clinical conditions, among them non-insulin-dependent diabetes mellitus, endometrial dysplasia and hypertension with insulin resistance, and polycystic ovary syndrome. The purpose of this study was to investigate the serum homocystein levels and other metabolic parameters in relationship with the MTHFR C677T gene polymorphism in patients with PCOS. Our study included 86 young women with PCOS constituting the study group and 70 healthy women constituting the control group.