Long noncoding RNAs and their possible roles in tumorigenesis and drug resistance in cancer chemotherapy.

Cancer is still one of the most important diseases that have a high mortality rate around the world. The management of cancer involves many procedures, which include surgery, radiotherapy, and chemotherapy. Drug resistance in cancer chemotherapy is considered one of the most important problems in clinical oncology. A good understanding of the tumorigenesis process and the mechanisms of developing chemotherapy resistance in cancer cells will help achieve significant advances in cancer treatment protocols. In recent years, there has been an increasing interest in long noncoding RNAs (lncRNAs). LncRNAs are no longer just a transcriptional noise, and many investigations proved their possible roles in regulating mandatory cellular functions. A lot of newly published studies confirmed the implication of lncRNAs in the tumor formation process and the multiple drug resistance in cancer chemotherapy. The main aim of this review is to focus on the lncRNAs' functions in the cell, their possible roles in the tumor formation process, and their roles in the development of chemotherapy resistance in different cancer cells.

Association between metformin and vitamin B12 deficiency in patients with type 2 diabetes.

Diabetes mellitus (DM) is still one of the most common diseases worldwide, and its prevalence is still increasing globally. According to the American and European recommendations, metformin is considered a first-line oral hypo-glycemic drug for controlling type 2 DM (T2DM) patients. Metformin is the ninth most often prescribed drug in the world, and at least 120 million diabetic people are estimated to receive the drug. In the last 20 years, there has been increasing evidence of vitamin B12 deficiency among metformin-treated diabetic patients. Many studies have reported that vitamin B12 deficiency is related to the ma-labsorption of vitamin B12 among metformin-treated T2DM patients. Vitamin B12 deficiency may have a very bad complication for the T2DM patient. In this review, we will focus on the effect of metformin on the absorption of vitamin B12 and on its proposed mechanisms in hindering vitamin B12 absorption. In addition, the review will describe the clinical outcomes of vitamin B12 deficiency in metformin-treated T2DM.

Diagnostic Performance of Erythropoietin and Erythropoietin Receptors Levels in Children with Attention Deficit Hyperactivity Disorder.

OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) is a heterogeneous, highly heritable, a common childhood neurobehavioural disorder resulting from complex gene-gene and gene-environment interactions. The erythropoietin (Epo)/erythropoietin receptors (EpoR) system turned out to have additional important functions in nonhematopoietic tissue. In this study, we aimed to investigate the levels of Epo and and EpoR, and also their diagnostic values in children with ADHD. METHODS: A total of 70 children were included in the study, 35 drug-naive patients with ADHD (age: 6-12 years; male/female: 20/15) and 35 healthy controls (age: 6-12 years; male/female: 22/13). Serum Epo and EpoR levels was determined using a commercial sandwich enzyme-linked immunosorbent assay kit. RESULTS: The results indicated that the levels of Epo decreased in patients with ADHD compared to control (p < 0.05). On the other hand, EpoR levels increased in these patients (p < 0.05). Furthermore, the ratio of Epo/EpoR was significantly lower in ADHD patients than controls (p < 0.05). Receiver operator characteristic curve analysis showed high diagnostic performance for Epo and EpoR, areas under curve were 0.980 and 1.000, respectively. CONCLUSION: This is the first report to investigate the association between serum Epo and EpoR levels in ADHD patients. Our results indicated that Epo may play a role in the etiology of ADHD, and Epo therapy may be beneficial in these disorders if given in addition to the routine treatment of children with ADHD. Furthermore, our results reveal possible diagnostic value of Epo and EpoR.

The effect of Rheum ribes L. on oxidative stress in diabetic rats.

Objectives Rheum ribes L. is a perennial plant that belongs to the family of Polygonaceae, which is often used in traditional therapy because it possesses many bioactivities, such as antioxidant and antibacterial ones. Here we examined the effect of different R. ribes L. extracts on oxidative stress in experimental diabetic rats. Methods Thirty-six rats were divided into six groups as follows: group I, control group; group II, diabetic rats; group III, diabetic rats treated with the aqueous extract of R. ribes L. by gavage at 50 mg/kg for 15 days; group IV, diabetic rats treated by gavage with the ethanolic extract of R. ribes L. at 50 mg/kg for 15 days; group V, nondiabetic rats treated by gavage with the aqueous extract of R. ribes L. at 50 mg/kg for 15 days; group VI, nondiabetic rats treated by gavage with the ethanol extract of R. ribes L. at 50 mg/kg for 15 days. After 15 days, the animals were sacrificed and the liver and kidney tissues of each animal were isolated. Superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) activities in the tissue samples were measured, and histopathologic examination was carried out. Results R. ribes L. was effective in reducing the oxidative stress and increasing the levels of the antioxidant enzymes. Increased levels of MDA and decreased levels of SOD, CAT and GSH-Px were observed in both the liver and kidney tissues in group II. Decreased levels of MDA and increased levels of SOD, CAT and GSH-Px were observed in group III compared with group II. In group IV, decreased levels of MDA and increased levels of SOD, CAT and GSH-Px were observed in comparison with group II. Conclusions Diabetes increases oxidative stress and causes a decrease in antioxidant enzyme levels. Both aqueous and ethanolic extracts of R. ribes L. decrease oxidative stress activity and increase the levels of antioxidant enzymes. The ethanol extract of R. ribes L. has a higher antioxidant effect than the aqueous extract.

Protective effect of N-acetyl cysteine against radiotherapy-induced cardiac damage.

Purpose: Although radiotherapy (RT) is an important component of cancer treatment, it induces adverse tissue reactions in the around of cancer tissue. Therefore, radioprotectives are needed to protect normal tissues. The aim of this study was to investigate the radioprotective effect of N-acetylcysteine (NAC) on RT-induced cardiac damage in rats for the acute term.Materials and methods: The animals were divided into four groups. The rats in control group were injected with saline for 7 d; the rats in NAC group were injected NAC at dose of 240 mg/kg d for 7 d; the rats in RT group were injected with saline for 7 d plus was irradiated 1 h after the last injection and the rats in NAC + RT group were injected with NAC for 7 d and irradiated 1 h after the last NAC dose. The electrocardiogram was recorded and evaluated PR interval, QRS duration, QT interval, T wave alterations and heart rate. Serum interleukin-4, interleukin-6, tumor necrosis factor-alpha, interleukin 1 beta, galectin-3 levels and creatine kinase and creatine kinase isoenzyme-MB activities were determined in all groups. Also, tissue malondialdehyde (MDA) and nitric oxide levels, superoxide dismutase, catalase and glutathione peroxidase activities were determined. In addition, histological changes of heart were evaluated. All measurements were performed 24 h after RT.Results: In the RT group, findings supporting cardiac injury were observed in the electrocardiogram. Also, cytokine levels and oxidative stress were significantly increased. Pretreatment of rats with NAC ameliorated cardiac injury induced by RT.Conclusions: Our findings suggested that NAC may be a potential radioprotector which is capable of preventing cardiac damage.

N-Acetylcysteine-induced vasodilatation is modulated by KATP channels, Na+/K+-ATPase activity and intracellular calcium concentration: An in vitro study.

BACKGROUND: In this study, we aimed to investigate the role of ATP-sensitive potassium (KATP) channel, Na+/K+-ATPase activity, and intracellular calcium levels on the vasodilatory effect of N-acetylcysteine (NAC) in thoracic aorta by using electrophysiological and molecular techniques. METHODS: Rat thoracic aorta ring preparations and cultured thoracic aorta cells were divided into four groups as control, 2mM NAC, 5mM NAC, and 10mM NAC. Thoracic aorta rings were isolated from rats for measurements of relaxation responses and Na+/K+-ATPase activity. In the cultured thoracic aorta cells, we measured the currents of KATP channel, the concentration of intracellular calcium and mRNA expression level of KATP channel subunits (KCNJ8, KCNJ11, ABCC8 and ABCC9). RESULTS: The relaxation rate significantly increased in all NAC groups compared to control. Similarly, Na+/K+- ATPase activity also significantly decreased in NAC groups. Outward KATP channel current significantly increased in all NAC groups compared to the control group. Intracellular calcium concentration decreased significantly in all groups with compared control. mRNA expression level of ABCC8 subunit significantly increased in all NAC groups compared to the control group. Pearson correlation analysis showed that relaxation rate was significantly associated with KATP current, intracellular calcium concentration, Na+/K+-ATPase activity and mRNA expression level of ABCC8 subunit. CONCLUSION: Our findings suggest that NAC relaxes vascular smooth muscle cells through a direct effect on KATP channels, by increasing outward K+ flux, partly by increasing mRNA expression of KATP subunit ABCC8, by decreasing in intracellular calcium and by decreasing in Na+/K+-ATPase activity.

MyD 88 Polymorphisms in Children Diagnosed with Sepsis.

BACKGROUND: Myeloid differentiation primary response gene 88 (MyD 88) is an intracellular adapter protein that mediates the early immune response to pathogens. Toll-like receptors (except TLR-3) induce the immune response through a MyD 88-dependent signal pathway. AIMS: We aimed to investigate the MyD 88 polymorphisms that play important roles in the immune response in septic children and to evaluate whether or not they were risk factors in the development of sepsis. STUDY DESIGN: Case-control study. METHODS: Sixty-five patients diagnosed with sepsis in the Pediatric Intensive Care Unit during the period from April 2010 to January 2012 were included as the study group. Sixty-five children without sepsis were included as controls. After DNA was obtained from blood samples in the study and control groups, MyD 88 polymorphisms were analyzed. According to the genotype and allele frequencies, the distributions of MyD 88 polymorphisms [Single nucleotide polymorphism (SNP) - 938 C/A (rs4988453), MyD 88 SNP 1944 C/G (rs4988457)] were analyzed in both the study and control groups. RESULTS: The C/C genotype of MyD 88 SNP -938 was significantly more common than the C/A genotype in the patient group (p=0.002). No statistically significant difference in the frequency of the MyD 88 SNP 1944 genotype was found between the study and control groups (p=0.272). CONCLUSION: Gene polymorphism studies could elucidate our understanding of sepsis in terms of prevalence and the management of treatment. It was shown in this study that children with the MyD 88 SNP -938 C/C genotype had a greater tendency toward sepsis. However, additional studies should be performed.

Hemoglobinopathies in the Çukurova Region and Neighboring Provinces.

To contribute to the creation of a mutation map of the region, we aimed to determine the mutation spectrum of thalassemias and abnormal hemoglobins (Hbs) in the Çukurova region and surrounding provinces. In this study, a total of 8135 samples from Adana, Hatay, Mersin, Konya and Kayseri provinces between 1993 and 2014 were analyzed. Complete blood cell (CBC) counts and Hb typing were carried out using automatic cell counters, cellulose acetate membrane electrophoresis and high performance liquid chromatography (HPLC), respectively. For the molecular analyses, genomic DNA was extracted using both manual and automated DNA extraction devices. Determination of Hb mutations were done by microarray, restriction fragment length polymorphism (RFLP), amplification refractory mutation system (ARMS) and gap-polymerase chain reaction (gap-PCR) methodologies. Samples were analyzed for abnormal Hb and thalassemia mutations. Out of 8135 samples, 1382 were observed to be carrying Hb mutations. It was identified that 826 mutation carriers included abnormal Hbs with a frequency of 59.7%, 416 carriers included ß-thalassemia (ß-thal) mutations with a frequency of 30.7% and 136 carriers included α-thalassemia (α-thal) mutations with a frequency of 9.9%. In this study, the most frequently observed abnormal Hb in the region was Hb S [ß6(A3)Glu→Val (GTG > GAG), HBB: c.20T > A], whereas the most commonly observed mutations were the IVS-I-110 (G > A) (HBB: c.93-21G > A) point mutation in ß-thal and the 3.7 kb deletion in α-thal.