Are adipocytokines inflammatory or metabolic mediators in patients with inflammatory bowel disease?

This study examined the adiponectin and leptin levels and insulin resistance (IR) in patients with inflammatory bowel disease (IBD) and the associations between these factors and IBD characteristics. Fasting serum leptin, adiponectin, glucose, and insulin levels, as well as inflammatory parameters, were measured in 105 patients with IBD (49 patients with Crohn's disease [CD], 56 patients with ulcerative colitis [UC]) and 98 healthy controls [HC]. IR was evaluated using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Disease activity and severity in patients with UC were evaluated using the Truelove-Witts index, and patients with CD were evaluated using the Crohn's Disease Activity Index. Serum adiponectin levels were found to be significantly lower in patients with CD and UC (p<0.001). Serum leptin levels were also found to be significantly higher in both the UC and CD groups (p<0.001). When HOMA-IR levels were compared, no significant difference was detected for either the CD or UC groups compared with the controls. In conclusion, it was shown that leptin levels increased and adiponectin levels decreased in patients with IBD, which is thought to be related to chronic inflammation. The effects of adipocytokines in patients with IBD with inflammatory and metabolic processes need to be investigated in further broader studies.

A Strong Relationship Between Oral Squamous Cell Carcinoma and DNA Repair Genes.

Single nucleotide polymorphisms of DNA repair genes alter protein function and modulate DNA repair efficiency in various cancers. The X-ray repair cross-complementing group (XRCC) is responsible for the repair of DNA base damage and single-strand breaks. The aim of our study was to investigate the association of XRCC1 Arg399Gln and XRCC3 Thr241Met polymorphisms with the susceptibility to develop oral squamous cell carcinoma (OSCC) in Turkish subjects. One hundred eleven patients with OSCC and 148 healthy controls were recruited for the study. Genetic analysis was performed using polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP). We found that the XRCC1 Arg399Gln Gln/Gln genotype and Gln allele were risk factors for OSCC. Also, Arg/Arg genotype and Arg allele had protective effects against OSCC. Relative to XRCC3 Thr241Met polymorphism, carrying homozygote variants (Thr/Thr and Met/Met) was related with elevated OSCC risk. However, the heterozygote genotype and Thr allele variants were shown to be protective against OSCC. We suggest that XRCC1 Arg399Gln Gln/Gln genotype, Gln allele, and homozygote variants of XRCC3 Thr241Met polymorphism may be a risk factor for predisposition of OSCC in Turkish. In addition, XRCC3 Thr241Met genotype could be associated with tumor size and level of daily smoking.

Apoptotic and genomic effects of corilagin on SKOV3 ovarian cancer cell line.

Corilagin is a member of the tannin family and has been isolated from traditional Chinese medicinal plants, such as Phyllanthus spp. Corilagin has anti-inflammatory, antioxidative, antiatherogenic, and antihypertensive effects in various experimental models. In this research, we aimed to investigate for the first time whether corilagin had apoptotic and genomic effects in ovarian cancer treatment in the same study. The potential apoptotic of corilagin was investigated using a WST1 cell proliferation test, caspase 3, and mitochondrial membrane potential JC1 assays in a time- and dose-dependent manner. Genomic changes in expression levels against corilagin treatment were measured using an Illumina human HT-12V4 BeadChip microarray. Bioinformatic data analyses were performed using GenomeStudio and Ingenuity Pathway Analysis software. The data of our study demonstrated that there were statistically significant time- and dose-dependent increases in caspase 3 enzymatic activity and loss of mitochondrial membrane potential in line with decreases in cancer cell proliferation. According to gene-ontology analysis, we found that adherens junctions, antigen processing and presentation, and the phosphatidylinositol signaling system were the most statistically significant networks in response to corilagin treatment on SKOV3 cells, in a time- and dose-dependent manner. The apoptotic and genome-wide effects of corilagin on ovarian cancer cells were examined in detail for the first time in the literature. The results of our study suggest that corilagin might have the potential to be used as a new treatment option for epithelial ovarian cancer.

Is Human Oxoguanine Glycosylase 1 Genetic Variant Successful Even on Oral Squamous Cell Carcinoma?

BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the most widespread cancer types that arise from different sites of oral cavity and has a 5-year survival rate. This study is aimed at investigating the human oxoguanine glycosylase 1 (hOGG1)-Ser326Cys and APE-Asp148Glu polymorphisms of DNA repair genes in OSCC. MATERIALS AND METHODS: We investigated the hOGG1-Ser326Cys and APE-Asp148Glu polymorphisms of DNA repair genes in the oral cavity. Genotyping was conducted using polymerase chain reaction-restriction fragment length polymorphism analysis based on 132 patients who were diagnosed as having OSCC and 160 healthy subjects. RESULTS: Individuals with the genotype hOGG1-Ser326Cys, Cys allele carriers, were found significantly more frequently in the patient group compared to the control group as increase in risk (p < 0.001). Furthermore, it was observed that there were significantly more individuals with the Ser allele in the control group (p < 0.001). Individuals with genotype APE-Asp148Glu were not statistically significant; however, they were still more in the control group and provided protection against the disease. CONCLUSION: Our findings showed that hOGG1-Ser326Cys Cys allele is statistically important and relevant with respect to the development of oral squamous cancer. In view of our results, further studies including expression levels are required in which hOGG1-Ser326Cys should be investigated as molecular biomarkers for the early prediction of squamous cell carcinoma.

Neuronal nitric oxide synthase polymorphisms in obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a mental disease characterized by recurrent and intrusive thoughts and repetitive behaviours that negatively affect the quality-of-life of the patients. Recent studies have implicated the participation of neuronal nitric oxide in OCD pathogenesis as a neurotransmitter modulator. AIMS: To identify whether variations in neuronal nitric oxide synthase (nNOS) genes may render individuals susceptible to OCD development. METHODS: This study examined nNOS polymorphisms in 100 OCD patients and 121 unrelated healthy controls by polymerase chain reaction and restriction enzyme digestion methods. RESULTS: nNOS 276 C + genotype incidence was significantly higher in OCD patients than controls and conferred a 2-fold increased risk for OCD. No significant differences were observed in frequencies of nNOS 84 genotypes between patients and controls. CONCLUSION: This study shows an association between nNOS gene polymorphism and OCD. Exact mechanisms by which nNOS gene variants contribute to OCD pathogenesis need to be further investigated.

Chemokine and Chemokine Receptor Polymorphisms in Bipolar Disorder.

OBJECTIVE: Bipolar disorder (BD) is a debilitating psychiatric disease with unknown etiology. Recent studies have shown inflammation as a potential contributing factor of BD pathogenesis. However, potential associations between chemokine and chemokine receptor polymorphisms and BD have been fundamentally understudied. To identify participation of chemokines in BD pathogenesis, we examined genetic variants of several chemokine and chemokine receptor genes. METHODS: The study population comprised 200 patients with BD and 195 age- and sex-matched healthy controls. Genotyping of monocyte chemotactic protein 1 (MCP-1) A2518G, CCR2 V64I, CCR5 Δ32, CCR5 A55029G, stromal cell-derived factor 1 (SDF-1) 3'A, and CXCR4 C138T polymorphisms was performed using polymerase chain reaction and restriction enzyme digestion. RESULTS: We found that CCR5-Δ32 II and CXCR4-C138T C+ genotype frequencies contributed to an increased risk for BD. However, no statistical significance could be obtained with these genotypes after Bonferroni correction. A significant asssociation was only found with MCP-1 GG and G+ genotypes, which were markedly more prevalent in patients with BD and these genotypes seemed to significantly increase the risk for BD even after Bonferroni correction. CONCLUSION: Our findings indicate an association between genetic variants of certain chemokine and chemokine receptor (especially MCP-1) genes and BD. The exact mechanisms by which these variants contribute to BD pathogenesis and their clinical implications need to be further investigated.

Chemokine gene variants in schizophrenia.

Background Chemokines are known to play a major role in driving inflammation and immune responses in several neuroinflammatory diseases, including multiple sclerosis, Alzheimer's disease and Parkinson's disease. Inflammation has also been implicated in the pathogenesis of schizophrenia. Aim We aimed to investigate a potential link between chemokines and schizophrenia and analyze the role of MCP-1-A2518G, SDF-1-3'A, CCR5-delta32, CCR5-A55029G, CXCR4-C138T and CCR2-V64I gene polymorphisms in the Turkish population. Methods Genotyping was conducted by PCR-RFLP based on 140 patients and 123 unrelated healthy controls to show the relation between chemokine gene variants and schizophrenia risk. Results Frequencies of CCR5-A55029G A genotypes and CCR5-A55029G AG genotypes were found higher in patients than the controls and even also CCR2-V64I WT: CCR5-A55029G A and CCR2-V64I 64I: CCR5-A55029G A haplotypes significantly associated according to Bonferroni correction. However, no significant association was found for any of the other polymorphisms with the risk of schizophrenia. Conclusions Our findings suggest that CCR5-A55029G polymorphisms and CCR2-V64I WT: CCR5-A55029G A and CCR2-V64I 64I: CCR5-A55029G A haplotypes might have association with schizophrenia pathogenesis.

Association Between Polymorphisms of DNA Repair Genes and Risk of Schizophrenia.

AIMS: DNA repair gene polymorphisms have recently been implicated as potential pathogenic contributors of mental disorders. The aims of our study were to investigate the participation of nucleotide and base excision repair mechanisms in schizophrenia and to identify novel candidate DNA repair susceptibility genes. MATERIALS AND METHODS: For these purposes, we genotyped apurinic/apyrimidinic endonuclease 1 (APE1), human 8-oxoguanine DNA N-glycosylase 1 (hOGG1), X-ray repair cross-complementation group 1 (XRCC1), XRCC3, xeroderma pigmentosum group D (XPD), and xeroderma pigmentosum group G (XPG) genes in schizophrenia subjects, their healthy relatives, and unrelated healthy controls. RESULTS: Carriers of XRCC1 glutamine (Gln), XRCC3 threonine (Thr), hOGG1 cysteine (Cys), and XPD lysine (Lys) alleles were significantly more frequent among the cohort of schizophrenia patients than in controls. In contrast, the frequencies of XRCC3 methionine (Met) and XPD Gln allele carriers and hOGG1 serine (Ser)/Ser genotype carriers were higher among controls than in patients, suggesting a possible protective role for these gene variants against schizophrenia. Moreover, healthy relatives had significantly higher frequencies of XRCC3 Thr+ and XPD Lys+ genotypes than unrelated healthy controls. Minor allele frequencies, haplotypes, and overtransmitted alleles of DNA repair genes were also identified. CONCLUSION: Our findings support XRCC1, XRCC3, hOGG1, and XPD as risk genes for schizophrenia and suggest that altered DNA repair functions may be involved in schizophrenia pathophysiology.

Distribution of monocyte chemoattractant protein-1 (MCP-1 A-2518G) and chemokine receptor (CCR2-V64Ι) gene variants in hyperbilirubinemic newborns.

Hyperbilirubinemia is one of the most crucial syndromes, which is characterized by high levels of bilirubin, especially when it occurs in newborns. Bilirubin has cytoprotective properties with an antioxidant function and plays several major roles in the inflammation process with its members such as chemokines. The monocyte chemoattractant protein-1 (MCP-1) is a member of the C-C chemokine family and it has been associated with the inflammatory process. There are no data on the chemokine and its receptor genotypes in hyperbilirubinemic newborns to show their distribution. The aim of this study is to investigate the genotypic relationship of MCP-1 and its receptor CCR2-V64Ι with hyperbilirubinemia in Turkish newborns. A total of 85 newborns were included in the study: 20 infants with hyperbilirubinemia (hyperbilirubinemic group) and 65 infants without hyperbilirubinemia (non-hyperbilirubinemic group). Genotyping of MCP-1 A-2518G and CCR2-V64Ι gene polymorphisms were detected by PCR-RFLP, respectively. MCP-1 GG genotype in patients was higher than the controls and this genotype had 2.69 times higher risk for hyperbilirubinemic neonates (P: 0.20). The frequency of MCP-1 A-2518G G+ genotype in patients was higher than the controls (55.0% and 38.5%, respectively). The results of our preliminary study suggest that MCP-1 G+ genotype has the ability to increase the hyperbilirubinemia risk of newborns. These results should be focused on to research on a larger scale to confirm the findings.

COX-2 gene variants in bipolar disorder-I.

BACKGROUND: Bipolar disorder-I (BD-I) is a complex illness, and multiple genes and environmental factors determine its pathogenesis. Several studies have ascertained that BD-I and inflammation are linked through shared genetic polymorphisms and gene expression, as well as altered cytokine levels. COX-2 gene polymorphisms affecting COX-2 levels may be associated with BD-I by altering the inflammatory response. SUBJECTS AND METHODS: We investigated COX-2-765G→C and COX-2-1195A→G gene polymorphisms, which might be related for BD-I. The present analyses are based on 180 subjects with bipolar I disorder-I and 170 non-bipolar subjects. Genotyping of COX-2 gene polymorphisms (COX-2-765G→C, COX-2-1195A→G) were detected by PCR-RFLP. RESULTS: We found a positive association of COX-2 gene variants for development of BD-I. There were statistically significant differences in COX-2-1195A→G genotypes and alleles between the controls and patients (p:0.000; p:0.000). The indivuals with COX-2-1195A→G AA genotype had seems to be associated for BD-I (p:0.000). CONCLUSIONS: It seems that there is a protective role of COX-2-1195A→G G+ genotype against BD-I (p:0.000). In addition, there was a weak linkage disequilibrium between COX-2-765G→C and COX-2-1195A→G polymorphisms. Our findings suggest that COX-2-1195A→G AA genotype may faciliate the development of BD-I.

The relationship between catechol-O-methyltransferase gene Val158Met (COMT) polymorphism and premorbid cannabis use in Turkish male patients with schizophrenia.

BACKGROUND/AIM: One of the risk factors for increasing psychotic disorders is the use of cannabis. It has been shown that the inactivation of dopamine and other catecholamines causes a common polymorphism generating substantial variations in COMT enzyme activity. We aimed to understand the role of cannabis in the etiology of schizophrenia with and without pre-morbid usage. PATIENTS AND METHODS: The study group consisted of 80 male patients and genotyping of COMT enzyme Val158Met gene polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: It was found that the Val/Val genotype is significantly higher in patients with premorbid cannabis use (88.9%) compared to patients without pre-morbid cannabis use (68.4%). Also, the mean total positive and negative syndrome scale (PANSS) score seen in the Val/Val genotype group is significantly higher than the scores of the patients with the Met allele. CONCLUSION: The findings from this study confirm the association between COMT Val158 Met polymorphism and pre-morbid cannabis use in causing schizophrenia.

Apoptotic Effects of Quercitrin on DLD-1 Colon Cancer Cell Line.

Quercetin, which is the most abundant bioflavonoid compound, is mainly present in the glycoside form of quercitrin. Although different studies indicated that quercitrin is a potent antioxidant, the action of this compound is not well understood. In this study, we investigated whether quercitrin has apoptotic and antiproliferative effects in DLD-1 colon cancer cell lines. Time and dose dependent antiproliferative and apoptotic effects of quercitrin were subsequently determined by WST-1 cell proliferation assay, lactate dehydrogenase (LDH) cytotoxicity assay, detection of nucleosome enrichment factor, changes in caspase-3 activity, loss of mitochondrial membrane potential (MMP) and also the localization of phosphatidylserine (PS) in the plasma membrane. There were significant increases in caspase-3 activity, loss of MMP, and increases in the apoptotic cell population in response to quercitrin in DLD-1 colon cancer cells in a time- and dose-dependent manner. These results revealed that quercitrin has antiproliferative and apoptotic effects on colon cancer cells. Quercitrin activity supported with in vivo analyses could be a biomarker candicate for early colorectal carcinoma.

Association of SUMO4 M55V and -94ins/del gene variants with type-2 diabetes.

AIM: There are two different types of diabetes mellitus, type 1 and type 2, with still unclear molecular mechanisms. In the present study, we aimed to investigate the role of small ubiquitin-like modifier 4 (SUMO4) M55V and nuclear factor kappa B1 (NFKB1)-94del/ins in type-2 diabetes mellitus. MATERIALS AND METHODS: We analyzed SUMO4 M55V and NFKB1-94del/ins variants in 104 patients with type-2 diabetes and 124 healthy controls using the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques. RESULTS: The number of SUMO4 M55V MM genotype and M allele carriers was significantly higher in patients compared to the control group; however, no efficiency results were found related to NFKB1-94del/ins polymorphism. CONCLUSION: It was found that SUMO4 M55V polymorphism and type-2 diabetes were significantly associated with a possible SUMO4 region to type-2 diabetes susceptibility. This preliminary study showed that the distribution of SUMO4 M55V and type-2 diabetes mellitus in Turkish patients may form the basis of future research.

Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer.

BACKGROUND AND AIMS: Quercitrin (QR; quercetin-3-O-rhamnoside) has been used previously as an antibacterial agent and has been shown to inhibit the oxidation of low-density lipoproteins and prevent an allergic reaction. Furthermore, it was demonstrated that quercitrin exerts protective effects against H2O2-induced dysfunction in lung fibroblast cells. However, the mechanisms of quercitrin effects on cancer cell proliferation and apoptosis is not well understood. The aim of this study is to investigate the cytotoxic and apoptotic effects of quercitrin and the molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer (NSCLC) cell lines. METHODS: Time- and dose-dependent antiproliferative and apoptotic effects of quercitrin determined by WST-1 cell proliferation assay, lactate dehydrogenase (LDH) cytotoxicity assay, determination of nucleosome enrichment factor, changes in caspase-3 activity, loss of mitochondrial membrane potential (MMP) and also the localization of phosphatidylserine in the plasma membrane. Changes in whole genome gene expression levels were examined by Illumina Human HT-12v4 beadchip microarrays. RESULTS: There were significant increases in caspase-3 activity, loss of MMP, and increases in apoptotic cell population in response to quercitrin in A549 and NCI-H358 NSCLC cells in a time- and dose-dependent manner. CONCLUSION: Our results demonstrated that genes involved in leukocyte transendothelial migration, cell adhesion and phosphatidylinositol signaling system pathways were the most statistically significant pathways in NCI-H358 and A549 cells. These results revealed that quercitrin has antiproliferative and apoptotic effects on lung cancer cells by modulating the immune response. After confirming its anticarcinogenic effects in vivo, quercitrin could be a novel and strong anticancer agent against NSCLC.

The role of components of the extracellular matrix and inflammation on oral squamous cell carcinoma metastasis.

OBJECTIVES: Oral squamous cell carcinoma (OSCC) accounts for about 90% of malignant oral lesions, and is identified as the most frequently occurring malignant tumour of oral structures. We aimed to investigate the genes and pathways related with metastasis on Turkish OSCC patients. MATERIALS AND METHODS: We performed whole genome expression profiling array on an Illumina platform. A total of 24 samples with 12 OSCC and 12-paired controls that had no tumour were included in the study. Hierarchic clustering and heat map were used for data visualisation and p-values assessed to identify differentially expressed genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Ingenuity Pathway Systems (IPA) analysis were performed to consider biologic meaning of differential expression of the genes between tumour and control groups. RESULTS: We identified 790 probe sets, corresponding to 648 genes that were effective in separating invasive and metastatic OSCC. Consequently, we found statistically relevant expression results on extracellular matrix members on MMPs such as MMP3, MMP10, MMP1 and MMP9; on laminin such as LAMC2, LAMA3 and LAMB3; several genes in the collagen family; and also on chemokines from the inflammation process. CONCLUSION: Statistically relevant expression changes for MMPs, laminins, collagens, and chemokines, which are components of the extracellular matrix and inflammation process, may be considered as a molecular biomarker for early prediction. Further studies are necessary to determine and understand the molecular mechanisms that underlie OSCC metastasis.

DNA repair gene variants in migraine.

AIMS: Migraine is a common and debilitating episodic disorder characterized by recurrent headache attacks associated with autonomic symptoms. It affects an estimated 12% of the population. The etiology of the underlying neurodegenerative process is widely unknown; however, oxidative stress is a unifying factor in the current theories of migraine pathogenesis. After demonstrating the observation that oxidative DNA damage is detectable in migraine disease, searching the role played by DNA repair systems in migraine diseases could bring us much significant information about the pathogenesis of migraine. We prospectively investigated whether DNA repair gene polymorphisms (XRCC1 Arg399Gln, XRCC3 Thr241Met XPD Lys751Gln, XPG Asp1104His, APE1 Asp148Glu, hOGG1 Ser326Cys) account for an increased risk of migraine. The present analyses are based on 135 case subjects with migraine disease and 101 noncase subjects. Genotyping of DNA repair gene polymorphisms (XRCC1 Arg399Gln, XRCC3 Thr241Met XPD Lys751Gln, XPG Asp1104His, APE1 Asp148Glu, hOGG1 Ser326Cys) was detected by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: We demonstrated that apurinic endonuclease (APE), X-ray repair complementing defective repair in Chinese hamster cells 3 (XRCC3), xeroderma pigmentosum D (XPD), and hOGG1 gene variants were associated with an increased risk for development of migraine disease (p<0.05). In contrast, no statistically significant differences were found in genotype distributions of X-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1) and XPG between migraine cases and controls (p>0.05). CONCLUSIONS: Our findings have suggested that APE1, XRCC3, XPD, and hOGG1 gene variants could facilitate the development of migraine disease.