Lung cancer is the most common type of cancer in the world and about 1 million people die from lung cancer every year in the world. Inflammation is an important factor in the onset, progression and ...metastasis of lung cancer. The most important regulators of inflammation are chemokines and chemokine receptors. Chemokines induce the proliferation of cancer cells and prevent their apoptosis. Chemokines may indirectly affect tumor growth by inducing growth and release of angiogenic factors from cells in the tumor microenvironment. CXCL12/CXCR4 are chemokine and chemokine receptors predicted to be involved in lung cancer pathogenesis. This study aimed to determine the relationship between CXCL12/CXCR4 gene variations and CXCL12 serum levels in disease pathogenesis in lung cancer. For this purpose, DNA samples isolated from 90 lung cancer patients (36 squamous cell carcinomas, 18 small cell carcinomas and 36 adenocarcinomas) and 90 control individuals were genotyped by PCR-RFLP method for CXCL12 (rs1801157) and CXCR4 (rs2228014). CXCL12 protein levels were determined from serum samples by the enzyme-linked immuno-sorbent assay (ELISA) method. Results were evaluated using IBM SPSS Statistics 21 software and FINNETI program. As a result, there was no significant difference between the genotype frequencies of the CXCL12 rs1801157 variant and the risk of lung cancer (P = 0.396). CXCR4 rs2228014 genotypes were significantly associated with lung cancer risk (P < 0.001). Lung cancer patients had significantly elevated serum CXCL12 levels than controls (P < 0.001). In conclusion, the rs2228014 variants localized on the chemokine receptors CXCR4 gene was found to be closely related to lung cancer risk.
Inflammation is the natural immunological response of an organism against any harmful, foreign or destructive effect to heal and repair damaged tissue. The nod-like receptor pyrin domain-containing-3 ...(NLRP3) inflammasome is one of the main components of the inflammatory mechanism and is associated with many inflammatory diseases, but it is also closely related to metabolic abnormalities, such as type 2 diabetes mellitus (T2DM), insulin resistance and obesity. NLRP3 activates inflammation and causes interleukin-1β release, exogenous and endogenous danger signals, as well as insulin resistance. In this direction, we focus on the gene structure of NLRP3 in diabetes and accordingly, we aim to determine the relationship between eight gene variations in the NLRP3 gene and T2DM. We investigated the rs10802501, rs10733113, rs10754558, rs10925026, rs10925027, rs35829419, rs4612666 and rs4925659 single-nucleotide polymorphisms of NLRP3 gene using the Sequenom MassARRAY system in 100 T2DM patients and 100 control individuals. There were no significant differences between T2DM risk and the genotype frequencies of rs10802501, rs10733113, rs35829419 and rs10925026 variants (p > 0.05). However, significant genotype frequencies were determined for rs10925027 (p = 0.0013) and rs4925659 (p < 0.001). For the risk allele G of the rs10754558 variant, significant differences were found in the heterozygous and dominant model (p = 0.036, p = 0.033). The genotype distribution of the rs4612666 variant was significant only in the heterozygous model (p = 0.047). In this hospital-based case-control study, rs10925027, rs4925659 and rs10754558 variants were found to be closely related to T2DM risk. The rs10925027 CC genotype, rs4925659 GG genotype, rs10754558 GG and GC+GG genotypes of the NLRP3 were determined as important risk factors for the T2DM.
Background and aim
NOD1/CARD4 and NOD2/CARD15 are members of the Nod-like receptor (NLR) family, and they contain a caspase recruitment domain (CARD). NLRs are located in the cytosol where they bind ...bacterial and viral ligands and play a key role in the innate and adaptive immune response, apoptosis, autophagy, and reactive oxygen species generation. NLR gene polymorphisms may shift the balance between pro- and anti-inflammatory cytokines and modulate the risk of infection, chronic inflammation, and cancer. NOD1/CARD4 and NOD2/CARD15 gene polymorphisms may also be associated with altered risks for many cancer types. The aim of our study was to evaluate the potential associations between lung cancer and NOD1/CARD4 and NOD2/CARD15 polymorphisms.
Method
The NOD1/CARD4 (rs5743336) and NOD2/CARD15 (rs2066847) SNPs were analyzed by PCR restriction fragment-length polymorphism analysis (PCR–RFLP) in 260 subjects (lung cancer patients:
n
= 160; healthy controls:
n
= 100) of Turkish origin. PCR products were digested with
Ava
I for rs5743336 and
Apa
I for rs2066847 and then visualized.
Results
Comparisons of the genotypes between control and lung cancer patients were performed by Chi-square tests. We found a significant difference in the genotypic distribution of the rs5743336 variant of NOD1/CARD4 between lung cancer patients and controls (
p
= 0.010,
χ
2
= 9.220). However, we did not identify any statistically significant difference for the p.Leu1007fsX1008 (rs2066847) genotype of NOD2/CARD15 between groups (
p
> 0.05).
Conclusion
According to our data, the rs5743336 variant of the NOD1/CARD4 gene may influence the diagnosis and treatment of lung cancer, whereas the rs2066847 variant of the NOD2/CARD15 gene is not associated with lung cancer risk in the Turkish population.
There is little information about the hepatoprotective effects of gallic acid against ischemia–reperfusion (I/R) damage. Animals were subjected to I/R. Gallic acid at doses of 50 and 100 mg/kg body ...weight (bw) were injected as a single dose prior to ischemia. Liver tissue homogenates were used for the measurement of malondialdehyde (MDA), catalase (CAT) and glutathione peroxidase (GPx) levels. At the same time alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were assayed in serum samples and compared statistically. While the ALT, AST, LDH activities and MDA levels were significantly increased, CAT and GPx activities significantly decreased in only I/R-induced control rats compared to normal control rats (
P
< 0.05). Treatment with gallic acid at a dose of 100 mg/kg bw significantly decreased the ALT, AST, LDH activities and MDA levels, and markedly increased activities of CAT and GPx in tissue homogenates compared to I/R-induced rats with no treatment group (
P
< 0.05). In oxidative stress generated by hepatic ischemia–reperfusion, gallic acid contributes partially an alteration in the delicate balance between the scavenging capacity of antioxidant defense systems and free radicals in favour of the antioxidant defense systems in the body.
Chronic inflammation triggers DNA damage and oncogenic mutations and causes tumor formation and tumor progression. One of the important components of the inflammatory response is Toll-like receptor ...(TLR) family. The objective of our study is to determine the relationship between rs4986790(+896A/G) and rs4986791(+1196C/T) gene polymorphisms and lung cancer risk. PCR-RFLP technique was carried out to identify the genotypes in 100 control individuals and 160 lung cancer patients. DNA extracted from peripheral blood samples were amplified and digested with
NcoI
and
HinfI
then visualized. We did not find any difference between genotype frequencies between controls and patients (
p
> 0.05) in rs4986790. But a significant difference between control group and patients with lung cancer as for genotype frequencies (
χ
2
= 4.19,
p
= 0.041) in rs4986791 variants was found. Our data indicate that any correlation was not found between rs4986790 polymorphism and lung cancer, while a correlation between rs4986791 and lung cancer has been determined and found to be associated with lung cancer risk.
Amaç: Bu çalışmada deneysel olarak, sıçanlarda oksidatif stres oluşturan kimyasal madde karbon tetraklorit (CCl4)'e karşı, antioksidan özelliği bilinen likopenin ne derece koruyucu etkisi olduğu ...araştırıldı.
Gereç ve Yöntemler: Çalışmada 3 aylık 32 adet Spraque Dawley soyu erkek sıçan kullanıldı. Sıçanlar eşit sayıda 4 gruba ayrıldı. İlk 10 günlük uygulamada, sadece IV. gruba likopen (5 mg/kg/gün) intragastrik (i.g) olarak verildi. İkinci 10 günlük uygulamada ise, I. gruba (kontrol) sıvı yağ (0.2 ml/kg/gün) intraperitoneal (i.p) ve (i.g), II. gruba CCl4 (0.2 ml/kg/gün) (i.p) , III. gruba likopen (5 mg/kg/gün) (i.g), IV. gruba likopen + CCl4 belirtilen dozlarda ve aynı saatlerde günde iki uygulama ile verildi. Madde uygulaması sona erdikten sonraki 24. saatte, eter anestezisi altında uygun teknikler kullanılarak karaciğer doku örnekleri alındı. Bu örneklerden hazırlanan homojenatta malondialdehit (MDA) düzeyi, katalaz (CAT) ve glutatyon peroksidaz (GSH-Px) aktiviteleri tayin edildi. Histolojik çalışmalar için alınan karaciğer doku örnekleri %10 nötral formalinde tespit edildi. Rutin takip sonrası kesitler H&E ile boyandı ve ışık mikroskobunda incelendi.
Bulgular: Çalışma sonunda, likopenin tek başına beklenildiği gibi kontrole benzer değerler verdiği görüldü. CCl4 verilen grupta ise, CCl4 metabolizmasına bağlı olarak, oluşan serbest radikallerin MDA düzeyini arttırdığı, böylece oksidatif hasarın oluştuğu tespit edildi. IV. grupta bu hasarın, likopen tarafından aktiviteleri arttırılan ve serbest radikal süpürücüleri olarak kabul edilen CAT ve GSH-Px tarafından, nispeten düzeltilerek kontrol değerlere yaklaştırdığı görüldü. Histolojik sonuçlarında kimyasal sonuçları desteklediği tespit edildi.
Sonuçlar: Sonuç olarak, likopenin farklı dozlarda ve kullanım süreleri ile önleyici ya da teropatik bir ajan olarak rolü hakkında önemli bilgiler sağlayacağı kanısındayız.
Objective: In this study, the protective effect of the antioxidant lycopene with respect to carbon tetrachloride (CCl4)-induced oxidative stress in rats was examined experimentally.
Material and Methods: In this study, thirty-two three month-old Spraque Dawley male rats were assigned to four groups in equal numbers. Group four received lycopene (5 mg/kg/day) intragastrically (i.g.) for a 10-day period as pretreatment. In the second 10-day period, group one received liquid oil (0.2 ml/kg/day) intraperitoneally (i.p.), group two CCl4 (0.2 ml/kg/day) (i.p.), and group three lycopene (5 mg/kg/day, i.g.). During this period, the previously-treated group four received the same dose of lycopene plus CCl4 daily in two divided doses. Within 24 hours of the last dose, liver tissue samples were collected for homogenate from the rats using appropriate techniques under ether anesthesia. Malondialdehide (MDA) levels were measured and catalase (CAT) as well as glutathione peroxidase (GPx) activities were determined. Tissue samples were fixed in 10% neutral formalin and slices were stained with H&E and examined under a light microscope in subsequent histological studies.
Results: Results showed, as expected, that the values obtained in the lycopene only treatment groups were close to values in the control group. In the CCl4 treated group, free radical formation secondary to CCl4 metabolism resulted in increased MDA levels and led to oxidative damage. This damage was corrected to levels comparable to those of the controls by the free radical scavengers CAT and GPx, the activities of which were noticeably increased secondary to lycopene treatments. Histological studies supported these biochemical results.
Conclusion: These results provide promising information regarding the ability of lycopene to act as a dose- and duration of use-dependant chemo-preventive or therapeutic agent.
Studies indicate that leptin is involved in not only energy expenditure and food intake, but also in protection against apoptosis, in inflammation and in stimulation of proliferation in many cell ...types. However, leptin treatment increases the oxidative stress in many cell culture studies. This contradiction evoked a question of whether leptin acts as an oxidant or antioxidant on glial cells. We investigated the effect of leptin on glial cell survival and hydrogen peroxide (H2O2)-induced toxicity in vitro. The survival rate of the cells was determined by using 3-(4,5-D-methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, thyazolyl blue (MTT) method. The cells obtained from the whole brain of 1â3 day-old rat were treated with 1, 10, 100 and 1000 ng/mL leptin for 24 or 72 h. Either the pretreatment of leptin alone for 5 h or leptin combined simultaneously with H2O2 or well known antioxidant glutathione (GSH) were applied to the cells. Malondialdehyde (MDA) levels were measured in cell lysates to which leptin was added for 24 h. The 100 and 1000 ng/mL leptin treatment for 72 h increased the glial viability by 19% and 36%, respectively. The dose of H2O2 that killed 75% of the cells was determined as 100 µM. GSH at different doses was applied as a positive control to the cells and the dose of 500 µM completely eliminated toxic effect of 100 µM H2O2. Either the pretreatment of leptin alone for 5 h or leptin combined simultaneously with H2O2 could not eliminate H2O2-caused toxicity. Furthermore, respective leptin doses did not change the glia MDA level. We suggest that leptin can increase glia survival dose dependently, but can not eliminate H2O2-induced oxidation in primary mixed glial cell culture.
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