Objective and design
Type 2 diabetes is a pandemic disease characterized by hyperglycemia, ineffective insulin use, and insulin resistance and affecting 1 in 11 people worldwide. Inflammation-related ...insulin resistance is thought to play an important role in the etiology of the disease. TLR4 is the central receptor of the natural immune system and has an important role as a trigger of the inflammatory response. The IRAK1 and TIRAP are members of the TLR4 pathway and involved in the TLR4-mediated inflammatory response. Genetic variants in the TLR4 gene or in the IRAK1 and TIRAP genes may have an important role in the development of insulin resistance and type 2 diabetes by disrupting the inflammatory response. In this direction, we aimed to investigate the relationship among TLR4 and IRAK1, TIRAP gene variants, and type 2 diabetes and insulin resistance, and investigate how these variants affect inflammatory factors (TNF-α, IL-6, MCP-1, and IL-1β).
Subjects and methods
In our study, a total of seven variations on the genes of TLR4 (rs4986790, rs4986791), IRAK1 (rs1059703, rs3027898, rs7061789), and TIRAP (rs8177374, rs8177400) were genotyped by the MassARRAY
®
Iplex GOLD SNP genotyping in 100 type 2 diabetic patients and 100 non-diabetic individual. The TLR4 rs4986790 and rs4986791 variation was confirmed by PCR–RFLP method also. The serum IL1-β, IL6, MCP-1, and TNF-α levels were measured using enzyme-linked immunosorbent assay kits.
Results and conclusion
As a result of our study, no correlation was found among TLR4, IRAK1, and TIRAP gene variants and the risk of type 2 diabetes and insulin resistance. However, TNF-α, IL-6, MCP-1, and IL-1β levels were also associated with diabetes and insulin resistance (
p
> 0.05). Although the gene variants were not significant in type 2 diabetes and insulin resistance groups, IRAK1, TLR4, and TIRAP gene variants were found to be associated with TNF-α, IL-6, MCP-1, and IL-1β levels.
The present study was aimed to investigate the relationship between NOD1/CARD4 and NOD2/CARD15 gene polymorphisms and osteoporosis in the Turkish population. The first time we thought that the ...functional polymorphisms in NOD1/CARD4 and NOD2/CARD15 genes might have triggered the development of osteoporosis. The objective of our study was to determine the relationship between NOD1/CARD4 and NOD2/CARD15 SNPs and osteoporosis. The NOD1/CARD4 (rs5743336) and NOD2/CARD15 (rs2066847) SNPs were analyzed by PCR restriction fragment length polymorphism (PCR-RFLP) in 94 healthy controls and 164 subjects with osteoporosis. PCR products were digested with restriction enzymes AvaI for NOD1/CARD4 and ApaI for NOD2/CARD15. We found that NOD1/CARD4 genotype distribution of AA, GA and GG were 15, 44 and 41% for patients and 17, 46 and 37% for controls, respectively. NOD2/CARD15 mutation was found only in three patients (1.8%) as heterozygote. The results did not show any statistical difference between NOD1/CARD4 and NOD2/CARD15 genotype distribution of patients and healthy groups (χ2 = 1.740, P=0.187; χ2 = 1.311, P=0.519). However, the most frequent AG genotype (46%) of NOD1/CARD4 was observed in healthy controls, GG genotype (44%) of NOD1/CARD4 was observed as the most frequent in osteoporotic patients. NOD2/CARD15 WT/WT genotype, the most frequent genotype, was observed in both groups. Statistical analysis revealed that NOD1/CARD4 and NOD2/CARD15 polymorphisms are not associated with osteoporosis. However, a definite judgement is difficult to be made due to restricted number of patients and small size of control group. Further research is sorely warranted in this direction.
What is known and objective
Type 2 diabetes (T2DM) is a multigenic disease that develops with impaired β‐cell function and insulin sensitivity and has a high prevalence worldwide. A cause often ...postulated for type 2 diabetes is chronic inflammation. It has been suggested that inflammatory regulators can inhibit insulin signal transduction and that inflammation is involved in insulin resistance (IR) and the pathogenesis of type 2 diabetes. In this direction, we aimed to investigate the gene variants of MyD88 (rs1319438, rs199396), IRAK4 (rs1461567, rs4251513, rs4251559) and TRAF6 (rs331455, rs331457) and serum levels of COX‐2, NF‐κB, iNOS in T2DM and IR.
Methods
The MyD88, IRAK4 and TRAF6 variations were genotyped in 100 newly diagnosed T2DM patients and 100 non‐diabetic individuals using The MassARRAY® Iplex GOLD SNP genotyping method. The COX‐2, iNOS and NF‐κB levels were measured in serum samples with the sandwich‐ELISA method. Results were analysed using SPSS Statistics software and the online FINNETI program.
Results and discussion
In our study, a total of the 7 variants in the MyD88, IRAK4 and TRAF6 genes were genotyped, and as a result, no relationship was found between most of these variants and the risk of type 2 diabetes and insulin resistance (p > 0.05). Only, the rs1461567 variant of the IRAK4 gene was significant in the heterozygous model (CC vs. CT), and the CT genotype was most frequent in diabetic individuals compared with the non‐diabetics (p = 0.033). Additionally, COX‐2 and iNOS levels were found to be associated with diabetes and insulin resistance (p < 0.05).
What is new and conclusion
Our results show that high COX‐2 and iNOS levels are associated with T2DM, besides MyD88, IRAK4 and TRAF6 gene variations may not be closely related to type 2 diabetes and insulin resistance. Nevertheless, studies in this pathway with a different population and a large number of patients are important.
Hypertension is a major health problem with increasing prevalence around the world. Tannic acid is water-soluble polyphenol that is present in tea, green tea, coffee, red wine, nuts, fruits and many ...plant foods. It has been reported to serve as an antioxidant or a pro-oxidant depending on the type of cells and its concentration. The purpose of our study was to evaluate the effect of tannic acid on systolic blood pressure, oxidative stress and some urinary parameters in the rat model of essential hypertension. Blood pressures of all rats were measured using the tail-cuff method. The nitric oxide synthase inhibitor N (omega)-nitro-L-arginine was administered orally at a dose of 0.5 g/l/day for 15 days to rats in order to create an animal model of hypertension. Tannic acid was intraperitoneally injected at a dose of 50 mg/kg for 15 days. Superoxide dismutase, catalase activity and the concentration of malondialdehyde (MDA) were determined in blood plasma and homogenates of heart, liver and kidney. In order to evaluate renal functions, urine pH, urine volume, urine creatine, uric acid, and urea nitrogen values were measured. Compared with the hypertension group, a decrease in MDA concentrations of heart tissue (
p
< 0.01), urea nitrogen values (
p
< 0.01) and urine volumes (
p
< 0.001) were established in hypertension + tannic acid group. There was also a decrease in blood pressure values (20th and 30th days) of this group, but there was no a statistical difference according to hypertension group. The findings of our research show the effect of tannic acid in lowering blood pressure in hypertensive rats.
Association of PTEN Gene Polymorphisms, Protein Levels and Endometrial Cancer: A Hospital-Based Case-Control Study Emine Yagci1, Hikmet Melike Ozturk1, Tufan Oge2, Cansu Ozbayer3, Hulyam Kurt1 ...0000-0003-2179-1318, 0000-0002-1951-9713,0000-0002-1120-1874, 0000-0003-2433-9925 1Eskisehir Osmangazi University, Faculty of Medicine, Department of Medical Biology, Eskisehir, Turkey. 2 Eskisehir Osmangazi University, Faculty of Medicine, Department of Gynecology, Eskisehir, Turkey. 3 Kutahya Health Sciences University, Medical Faculty, Department of Medical Biology, Kutahya, Turkey. Corresponding Author: Emine Yagci, Telephone: +90 (222) 2392979/4598, e-mail adress: eminetsci@gmail.com Abstract Endometrial cancer is a type of cancer that develops in the inner lining of the uterus, called the endometrium. After breast, lung, and colon cancer, endometrial cancer is the most prevalent malignancy of the female genital system in industrialized nations like North America and Europe. Phosphatase and Tensin homolog (PTEN), deleted on chromosome 10, is a tumor suppressor gene located on chromosome 10q23.31, which encodes a 403 amino acid protein with both lipid and protein phosphatase activities. One of the most common genetic abnormalities identified in human malignancies are somatic mutations in the PTEN gene. The tumor suppressor activity of the PTEN enzyme is reduced or completely lost as a result of PTEN gene mutations. Considering this information, it is thought that PTEN gene polymorphisms may be associated with the pathogenesis of the disease. The purpose of our study is to determine the relationship between functional PTEN polymorphisms IVS4 (–/+) and -9 C/G and endometrial cancer. DNAs belonging to 63 endometrial cancer patients and 63 control individuals were genotyped by PCR-RFLP method for 2 genetic variants of PTEN IVS4 (–/+) and -9 C/G gene. The expression level of PTEN protein was measured by the Elisa method from serum samples. Our results were evaluated with appropriate statistical methods. As a result of our study, no statistically significant difference was found in the risk of endometrial cancer and genotype frequencies of –9 C/G and IVS4 (-/+) variants (p> 0.05). It was detected that the serum level of PTEN lessened significantly in patients with endometrial cancer in comparison to the control (p <0.001). As a consequence, there was no evidence that the PTEN gene variations -9 C/G and IVS4 (-/+), whose efficacy we examined in our investigation, increased the incidence of endometrial cancer in the Turkish population. However, endometrial cancer patients were shown to have lower serum levels of the tumor suppressor protein PTEN. Keywords: Endometrial cancer, PTEN, polymorphism, IVS4 and -9C/G.
Amaç: Osteoartrit (OA); kıkırdak yapımı ve yıkımı arasındaki dengenin bozulması ile ortaya çıkan, biyokimyasal ve morfolojik değişiklikler ile karakterize bir hastalıktır. Anjiyogenez ve inflamasyon ...süreçlerinin OA’in gelişmesi ve ilerlemesiyle ilişkili olduğu düşünülmektedir. Yapılan araştırmalar vasküler endotelial büyüme faktörü (VEGF) ve hipoksi ile indüklenen faktör (HIF) gibi anjiyogenik faktörlerin OA’nın gelişiminde rol oynayabileceğini göstermektedir. Bu çalışmada OA hastalarının peripheral mononüklear kan hücrelerinde (PMKH) VEGFA ve HIF1A gen ekspresyon seviyelerinin belirlemesi ve bu genlerin hastalığın evreleri ile olan ilişkisinin ortaya çıkarılması amaçlanmıştır. Yöntem: Diz osteoartriti tanısı almış 97 hasta ve 41 sağlıklı gönüllünün PMKH’lerinde VEGFA ve HIF1A mRNA ekspresyonları kantitatif real-time PCR (qRT-PCR) ile araştırıldı. Gönüllülerden alınan periferik kan örneklerinden PMKH'leri yoğunluk gradyanlı santrifüjleme ile izole edildi. Elde edilen hücrelerden cDNA sentezi sonrası spesifik primer-prob setleri kullanılarak qRT-PCR ile gen ekspresyon seviyeleri belirlendi. Bulgular: Hasta ve kontrol grupları arasında VEGFA ve HIF1A gen ekspresyonları arasında pozitif bir korelasyon (p<0.001) vardı. Bunun yanında, VEGFA ve HIF1A gen ekspresyon seviyelerinin, hasta ve kontrol grubu arasında (p>0.05) ve hastalığın evreleri arasında (p>0.05) istatistiksel olarak fark göstermediği belirlendi. Sonuç: Çalışmamızda OA PMKH’lerinde VEGFA ve HIF1A gen ekspresyonlarının birbiriyle ilişkili olduğu gösterilmiştir. Çalıştığımız gen ekspresyonları evrelerine göre diz osteoartritinin tanısında biyokimyasal marker olarak yeterli olamasa da, yapılacak ileri çalışmalarla potansiyel terapötik hedef olarak hizmet edebileceği kanısına varılmıştır.
Aim: Osteoarthritis (OA); is a disease characterized by biochemical and morphological changes caused by disruption of the balance between cartilage production and destruction. Angiogenesis and inflammation have been shown to be closely related processes to the development and progression of OA. Related research has shown that angiogenic factors such as vascular endothelial growth factor (VEGF) and hypoxia-induced factor (HIF) may play a role in the development of OA. The aim of this study was to determine the levels of VEGFA and HIF1A gene expression in peripheral mononuclear blood cells (PBMC) of OA patients and to determine the relationship between these genes and disease grades. Method: VEGFA and HIF1A mRNA expression in PBMCs of 97 patients with knee osteoarthritis and 41 healthy volunteers were investigated by quantitative real-time PCR (qRT-PCR). PBMCs were isolated from the peripheral blood samples from volunteers by density gradient centrifugation. Gene expression levels were determined by qRT-PCR using specific primer-probe sets after cDNA synthesis from the obtained cells. Results: There was a positive correlation (p <0.001) between VEGFA and HIF1A gene expressions between patient and control groups. In addition, VEGFA and HIF1A gene expression levels were not statistically different between the patient and control groups (p> 0.05) and between the grades of the disease (p> 0.05). Conclusion: In our study, it was shown that VEGFA and HIF1A gene expressions are correlated in OA PBMCs. Although the gene expression we studied was not sufficient as a biochemical marker in the diagnosis of knee osteoarthritis, it was concluded that it could serve as a potential therapeutic target with further studies.Keywords: Osteoarthritis, VEGFA, HIF1A, PMKH, Gene Expression
Type-2 diabetes (T2DM) is a metabolic disorder characterized by long-term insulin resistance, impaired insulin secretion from
β
-cells, and loss of beta cell mass and function. Inflammation and ...oxidative stress play a key role in the development of diabetes and are associated with insulin resistance. Notably, recent studies have demonstrated an association between body iron stores, insulin resistance and T2DM. Free iron, a powerful pro-oxidant molecule, is involved in oxidative stress, lipid peroxidation and endothelial dysfunction via its ability to generate free radicals. Specifically, the accumulation of iron in beta cells triggers oxidative stress and DNA damage, which have been reported to be associated with
β
-cell death and apoptosis. Solute carrier family-11 member-2 (SLC11A2) functions to transport ferrous iron and some divalent metal ions throughout the plasma membrane and across endosomal membranes. Functional polymorphisms in the
SLC11A2
gene have been reported to cause excess storage of iron, resulting in iron overload. In this study, we evaluated the association between T2DM and
SLC11A2
gene variants IVS4+44C/A, 1303C/A and 1254T/C by performing PCR-RFLP analysis on 100 T2DM patients and 100 healthy subjects. PCR products were digested with
Mnl
I
, Mbo
I and
Sfa
nI restriction endonucleases and the products were then separated by 3% agarose gel electrophoresis. The genotype frequencies of the 1254T/C and 1303C/A
SLC11A2
gene variants did not differ between healthy controls and T2DM patients (
P
>
0.05
). But, in recessive model (
P
=
0.037
) and homozygous CC genotype (
P
=
0.030
) for IVS4+44C/A showed significant correlation with T2DM risk. It is thought that presence of C allele of IVS4+44C/A plays pathological roles.
Cadmium (Cd) is among the heavy metals causing environmental pollution and can cause temporary or permanent oxidative stress in the cells. Antioxidative enzyme mechanisms may be inadequate in the ...response of living organisms to oxidative stress caused by these toxic substances. In this study, in order to prevent Cd induced oxidative stress, the possible protective effects of (TA), cacao oil (CO) and St. John's Wort oil (JWO) on lipid erythrocytes and antioxidant enzymes were investigated. We prepared packed erythrocytes from the blood samples of 7 healthy volunteers. Experiment groups consisting of control, Cd, TA, CO, JWO and their combinations (Cd+TA, Cd+CO ve Cd+JWO) were arranged. In all groups, malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) were measured. Comparisons between groups of normally distributed variable were evaluated by One-Way variance analysis (ANOVA). Comparisons between groups of not normally distributed variable wereevaluated by Kruskal-Wallis test. After Cd administration SOD activity was increased in TA (3507± 68.2 u/gHb), CO (3518 ±170.0 u/gHb) and JWO (3469±249.5 u/ gHb) groups compared to Cd group. After Cd administration MDA levels were decreased in CO (52,1±24,3 nmol/gHb) and JWO (54,1±23,7 nmol/gHb) groups compared to Cd group. However, it did not change in the TA (61,5±50,0 nmol/gHb) group. After Cd administration CAT activity was increased in TA (228,2±31,3 u/gHb), CO (281,6±295,3 u/gHb) and JWO (267,8±69,4 u/gHb) groups compared to Cd group (196,2±223,0 u/gHb). These results indicate that HF and SCI may reduce Cd-induced oxidative stress, but TA is not very effective in terms of MDA levels. These data obtained in terms of other studies may be guiding.
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