Tissue p53-induced glycolysis and apoptosis regulator (TIGAR) is associated with oxidative stress in benign and malignant colorectal lesions

Background: Colorectal cancer (CRC) is the fourth leading cause of cancer-mortality worldwide. Tissue p53-induced glycolysis and apoptosis regulator gene (TIGAR) has an important role in cellular glycolysis and acts as an oncogene.Objectives: We aimed to investigate the diagnostic utility of TIGAR in both CRC and benign bowel deceases.Methods: One-hundred-eighty tissue samples were recruited and classified into 3 groups: group (1) 60 CRC samples from the tumor mass of colorectal cancer patients, group (2), 60 non-neoplastic colorectal tissue samples and group (3), 60 benign bowel lesions samples (ulcerative-colitis, Chron’s disease, adenoma, and familial adenomatous polyposis). The expressions of tissue mRNA and protein levels of TIGAR were determined. Levels of malondialdehyde and reduced glutathione were also measured.Results: Our results showed upregulated expressions of TIGAR gene and protein levels in CRC tissues and benign colonic lesions compared to non-tumor tissues (p < 0.0001). Their levels were higher in inflammatory bowel diseases compared to non-inflammatory benign lesions. There were significant relations among TIGAR expression, protein levels, TNM staging, and the presence of metastasis (p<0.0001). ROC curve analysis showed that TIGAR mRNA expression and its protein can discriminate between CRC and benign lesions and between benign bowel disease and controls.Conclusions: To the best of our knowledge this is the first study to assess the level of TIGAR in different benign bowel diseases. TIGAR might be involved in the pathogenesis of benign and malignant bowel diseases and could be a potential biomarker for diagnosis

Epidemiology, risk factors, outcomes, and role of Serpin A3 as a biomarker for transition of acute kidney injury to chronic kidney disease in critically ill patients

Abstract Background Several studies have suggested a causal link between acute kidney injury and the consequent development of chronic kidney disease. The severity, frequency, and duration of acute injury are key factors in this process. Aims This study aimed to determine the epidemiology and outcomes of AKI to CKD transition in critically ill adult patients and to study the role of Serpin-A3 in the early recognition of AKI to CKD transition. Methods In this prospective observational study, a total of 252 patients attending Assiut University Hospitals Critical Care Unit and developed AKI during their stay were recruited. Serum and urinary Serpin A3 were measured by ELISA Kit. Complete blood picture, kidney function tests, urine analysis, serum electrolytes (serum sodium, potassium, calcium, phosphorus, and magnesium), liver function test, coagulation profile, C-reactive protein, 24-h urinary protein or urinary albumin/creatinine ratio, abdominal ultrasound were assessed for all the recruited participants. Follow-up was done for three consecutive months and after 3 months using serum creatinine, BUN, and serum potassium. Results It was found that old age is a risk factor for CKD following AKI, i.e., with 1-year increase in the patient’s age, there was 3% increase in the chance of transition. Significant association was found between rate of comorbidity and transition status. Also, cases with either infection or IV radio contrast exposure were 2.8 and 6.5 times more liable for transition. Cases with transition in this study had significantly higher renal function parameters. Higher median levels of Serpin A3 either serum or urinary was reported in transition patients. Improvement was reported in two-third of those without transition, and higher mortality rate was recorded in those without transition. Conclusion The frequency of transition was 20%. Older age, male gender, cardiac and CVS disease, the presence of infection, higher BUN and creatinine level, higher median K and PO4 levels, and higher median levels of Serpin A3 are risk factors for transition from AKI to CKD

Obesity Risk Prediction among Women of Upper Egypt: The impact of FTO rs17817449 gene polymorphism, serum ghrelin and high sensitivity C- reactive protein

Obesity is one of the main threats to the human health. It is a major risk factor for hyperinsulinemia, hypertension, hyperlipidemia, type II diabetes mellitus, and atherosclerotic cardiovascular disease. FTO gene variants have been associated with obesity and diabetes mellitus in different populations, but its role in the susceptibility of these diseases remains unknown. The present study is undertaken to assess the contribution of the FTO rs17817449 gene variants towards obesity and diabetes development and to evaluate the role of ghrelin and hs- CRP on the outcome of obesity in the Upper Egyptian women. A total of 229 subjects, 115 obese (65 non diabetics, 50 diabetics) and 114 non obese non diabetic controls were included in this case control study. Genotyping of FTO gene rs17817449 (T>G) polymorphism was performed by mutagenically separated PCR (MS-PCR) method. Estimation of serum gherlin, hs-CRP levels, related anthropometric and metabolic parameters were performed. The results revealed higher frequency of FTO rs17817449 G allele among obese subjects (46.5%) and obese diabetics (45%) compared to the controls (33.3%) which comprise about 1.75 times increase in the risk for obesity (p<0.01). The distribution of the GG and TG genotypes of FTO were 25.2%, and 42.6% among obese non diabetic, 24% and 42% among obese diabetic and 14.9% and 36.8% among controls respectively. FTO-GG genotype variant was significantly associated with weight, BMI and waist and hip circumference (p<0.05 for each). FTO GG carriers had 2.54 times the possibility to have obesity more than TT carriers. Ghrelin levels were significantly decreased and hs-CRP levels were significantly increased in obese subjects compared to the controls (P<0.001 for each). There was a significant negative correlation between serum ghrelin and hs-CRP (p<0.05). No significant association was detected between FTO genotypes and each of ghrelin, hs-CRP, lipid profile, fasting glucose or insulin levels. In conclusion, the G allele of FTO rs17817449 genotyping is associated with increased obesity risk but there is a lack of association with diabetes. It is also associated with some obesity indices as BMI, hip and waist circumference in the Upper Egyptian women. Both Ghrelin and hs- CRP could play a role in developing obesity. To the best of our knowledge, this is the first study of FTO SNP in Upper Egyptian women. Switching off this FTO faulty gene variant by the recent therapies (as certain foods or gene therapy) will prevent the percentage of women who is affected by this risk allele to get obese via burning rather than storing energy.Key words: FTO gene polymorphism, ghrelin, hs-CRP, Obesit