Biomarkers for Kidney-Transplant Rejection: A Short Review Study.

Kidney transplantation is the preferred treatment for end-stage renal failure, but the limited availability of donors and the risk of immune rejection pose significant challenges. Early detection of acute renal rejection is a critical step to increasing the lifespan of the transplanted kidney. Investigating the clinical, genetic, and histopathological markers correlated to acute renal rejection, as well as finding noninvasive markers for early detection, is urgently needed. It is also crucial to identify which markers are associated with different types of acute renal rejection to manage treatment effectively. This short review summarizes recent studies that investigated various markers, including genomics, histopathology, and clinical markers, to differentiate between different types of acute kidney rejection. Our review identifies the markers that can aid in the early detection of acute renal rejection, potentially leading to better treatment and prognosis for renal-transplant patients.

Possible roles of methylenetetrahydrofolate reductase polymorphism and folate status in patients with early hepatitis C virus genotype 4.

BACKGROUND AND STUDY AIMS: Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide. In Egypt, 92.5% of HCV infection cases reportedly involve infection with HCV genotype 4. HCV infection may induce liver steatosis directly and indirectly. Host genetic polymorphisms may also contribute to the pathogenesis of steatosis. Folate deficiency indirectly cuase liver damage. Folate status is mostly affected by MTHFR C677T polymorphism. The pathophysiology of thrombocytopenia (TCP) in HCV infection remains unclear. Thus, the present study investigated the roles and consequences of MTHFR C677T SNP and folate status in patients with early HCV genotype 4 infection and their relation with steatosis and thrombocytopenia. PATIENTS AND METHODS: Fifty patients with the HCV genotype 4 and 50 healthy controls were enrolled in the study. All the participants underwent laboratory, demographic, and anthropomorphic examinations. Serum folate level was determined, and genomic analysis of MTHFR C677T SNP was performed. RESULTS: No significant difference in allelic frequency of MTHFR C677T was observed between patients and controls. However, significantly lower serum folate level, hemoglobin level, and platelet count were found in patients than controls (p = 0.014, p = 0.005, and p = 0.001, respectively). The cholesterol, triglyceride, and high-density lipoprotein levels were also significantly lower in patients than controls (p < 0.001, p = 0.001, and p < 0.001, respectively), whereas the low-density lipoprotein level was significantly higher in patients (p < 0.001). Patients harboring the MTHFR CT genotype had a significantly lower serum folate level (p = 0.033) than the controls. Among the patients with HCV infection, those with the TT genotype had the highest body mass index (p = 0.003) and levels of cholesterol, triglyceride, and high-density lipoprotein (p = 0.007, p = 0.025, and p = 0.040, respectively). CONCLUSION: MTHFR C677T SNP may contribute to the development of complications associated with early HCV genotype 4 infection, such as dyslipidemia and decreased folate levels.

Effect of a weight loss program on serum adiponectin and insulin resistance among overweight and obese premenopausal females.

BACKGROUND: Obesity has emerged as a public health crisis in many populations including Egypt. Adipose tissue produces a number of adipokines, one of them is adiponectin which has attracted much attention because of its antidiabetic and antiatherogenic effects. OBJECTIVE: To determine the effect of a weight loss program on serum adiponectin level and insulin resistance among overweight and obese adult premenopausal females. STUDY DESIGN: A pre-postintervention study was carried out among 95 premenopausal overweight and obese females (body mass index ≥ 25 kg/m2) aged 20 to 40 years at the integrated health clinic affiliated to the High Institute of Public Health, Alexandria, Egypt, from February 2016 to February 2017. All participants underwent a weight loss program based on a reduced calorie balanced diet and advised to increase their physical activity. Dietary instructions and follow-up were done weekly throughout 16 weeks. Blood samples were collected to investigate serum adiponectin level and insulin resistance at the beginning and the end of the intervention. RESULTS: After 16 weeks, a significant decrease in body weight by 9.7% was associated with a significant increase in serum adiponectin from 13.3 ± 4.9 µg/ml to 18.5 ± 5.6 µg/ml. Both fasting insulin and insulin resistance had decreased significantly by 13.6% and 13.7%, respectively. CONCLUSION: A weight reduction program depending on a reduced calorie diet for 16 weeks was associated with a significant increase in total adiponectin level and reduction in insulin resistance. An emphasis on the importance of keeping normal weight through nutritional education and the promotion of healthy diets is recommended to reduce the risk of occurrence of insulin resistance, type 2 diabetes, and cardiovascular diseases.

Study of Dickkopf-1 (DKK-1) in patients with chronic viral hepatitis C-related liver cirrhosis with and without hepatocellular carcinoma.

AIM OF THE STUDY: Dickkopf-1 (DKK-1) is a secreted protein which acts as an inhibitor of Wnt/ß-catenin signaling. DKK-1 was found to be a helpful biomarker for many cancers including hepatocellular carcinoma (HCC). HCC is multifactorial in origin and its main etiology in Egypt is attributed to chronic hepatitis C virus (HCV) infection. Objectives: To assess the serum level and diagnostic performance of DKK-1 and α-fetoprotein (AFP) in Egyptian patients with chronic HCV-related liver cirrhosis with and without HCC. MATERIAL AND METHODS: 80 subjects were divided into: a control group (group I, 20 healthy volunteers) and two patient groups: group II (HCV with liver cirrhosis, 30 patients), and group III, (HCV-related liver cirrhosis with HCC, 30 patients). Thorough physical examination, triphasic computed tomography, calculation of Child-Pugh score, laboratory investigations (complete blood picture, liver profile, hepatitis B surface antigen, anti-HCV antibodies, AFP (chemiluminometry) and DKK-1 (ELISA) were performed. RESULTS: There was a significant decrease in DKK-1 level in HCV patients with liver cirrhosis (group II) and HCV patients with HCC (group III) compared to the control group (group I) (p < 0.001). However, there was a significant increase in DKK-1 level in HCV patients with HCC (group III) compared to HCV patients with liver cirrhosis (group II) (p < 0.033). The ROC curve showed that DKK-1 has less sensitivity but higher specificity in HCV patients with HCC (group III) compared with HCV patients with liver cirrhosis (group II). CONCLUSIONS: The combination of DKK-1 and AFP could further improve the diagnostic accuracy of HCV-related cirrhosis with or without HCC.

Methylation of Glutathione-S-Transferase P1 Promotor in Egyptian Females with Breast Cancer.

Background: Breast cancer (BC) is the second most common cancer after the lung cancer worldwide and number one killing cancer in Egyptian females . It is a multifactorial disease driven by different environmental, hormonal, genetic and epigenetic factors. Epigenetic alterations have been studied in cancer breast. Role of GSTP1 promotor methylation in breast cancer has been studied in different ethnic groups. Objectives: Current study aimed at studying the methylation status of the promotor region of glutathione-S-transferase P1 in breast ductal carcinoma of a cohort group of Egyptian females and its correlations with histopathological and prognostic parameters. Methods: Control group included 15 fresh normal breast tissues taken from BC female patients after leaving a clearly defined safety margin and a Patient group included confirmed 35 fresh breast ductal carcinoma tissue biopsies taken from female patients postoperatively. To all patients clinical examination, radiological examination (plain X-ray chest and or CT scan, ultrasonography of abdomen and pelvis were done), in addition to histopathological examination, typing, grading and staging of tumour, hormonal receptors status and molecular typing of breast mass. GSTP1 methylation status was evaluated using methyl specific polymerase chain reaction. Results: Statistical significant increase was found in methylation status of GSTP1 promotor gene in BC cases than that in control group, (60% of patients samples had methylated GSTP1 promotor vs only 6.7% of controls) (p= >0.001). No association was found between GSTP1 promotor methylation status and the poor prognostic factors neither with hormonal profile nor molecular type. However, GSTP1 promotor methylation were two times higher in postmenopausal than premenopausal cases and three times higher in late grade (III). Also GSTP1 promotor methylation was 2.4 times higher in Her2 positive cases than either ER or PR positive cases. Conclusion: Glutathione-S-Transferase P1 Promotor methylation plays a role in breast cancer development.

Possible association of ghrelin/obestatin balance with cardiometabolic risk in obese subjects with Helicobacter pylori.

OBJECTIVES: Helicobacter pylori (H. pylori) is a common gastric infection associated with extragastric conditions. The association between H. pylori infection and obesity is unclear. H. pylori may affect gut hormones involved in food intake and energy expenditure. The aim of this study is to evaluate ghrelin/obestatin balance and leptin in obese subjects with H. pylori infection. METHODS: Sixty healthy volunteers were divided into: obese and non-obese groups. Each group was divided into H. Pylori positive or H. pylori negative. Anthropometric parameters, H. pylori status, serum glucose, insulin level, and lipid profile were estimated with calculation of Homeostasis Model Assessment Insulin Resistance (HOMA-IR). Serum levels of ghrelin, obestatin, and leptin were evaluated. RESULTS: Significant increase was found in serum glucose, insulin and HOMA-IR ratio in obese subjects with positive H. pylori as compared to other groups. H. pylori positive obese subjects showed significantly increased ghrelin, ghrelin/obestatin balance, and leptin with a significant decrease in obestatin as compared to negative subjects. Ghrelin/obestatin ratio positively correlated with weight, body mass index, waist, glucose, insulin, HOMA-IR, leptin, cholesterol, triglycerides, low density cholesterol and also with H. pylori antigen in the same group. CONCLUSIONS: It can be concluded that ghrelin, obestatin, and leptin are affected by presence of H. pylori seropositivity in obese subjects. The higher ghrelin levels and ghrelin/obestatin ratio with lowered obestatin could be considered as a gastro-protective effect against inflammation induced by H. pylori.

Aldose reductase (-106) C/T gene polymorphism and possibility of macrovascular complications in Egyptian type 2 diabetic patients.

INTRODUCTION: Over the past three decades, the number of people with diabetes mellitus (DM) has more than doubled globally, making it one of the most important public health challenges to all nations. Aldose reductase (AR) is a rate-limiting enzyme in the polyol pathway, which has been implicated in the pathogenesis of diabetic microvascular complications; however, the association of the AR gene with diabetic macrovascular complications has rarely been investigated. AIM: The study aimed to identify the possible association between C(-106) T polymorphism of the AR gene and diabetic macroangiopathy in a cohort of Egyptian patients with type 2 DM. SETTINGS AND DESIGN: This study was conducted on 100 Egyptian subjects, the control group (n = 20) and the patient group (n = 80) with type 2 diabetes which were further subdivided into two subgroups with (n = 48) and without macroangiopathic complications (n = 32) as evidenced by carotid intima-media thickness, electrocardiography (ECG) ischemic changes, cerebrovascular insufficiency, and peripheral vascular insufficiency. SUBJECTS AND METHODS: All studied subjects were subjected to detailed history taking, clinical examination, ECG, carotid ultrasonography, routine laboratory investigations, and molecular studies including the detection of AR C(-106) T gene polymorphisms using the polymerase chain reaction (PCR)/restriction fragment length polymorphism technique. RESULTS: The genotype distribution and allele frequency of AR C(-106) T showed no statistical significance also the genotypes were not associated with any of the different studied parameters. CONCLUSIONS: The results suggest that the C(-106) T polymorphism in the AR gene is not involved in the pathogenesis of macroangiopathy in type 2 diabetes.