Apelin Serum Level in Egyptian Patients with Chronic Hepatitis C

Objective. Highlighting the apelin system would present a new therapeutic target for liver disease. Apelin; endogenous ligand for the orphan receptor APJ, was recently suggested to be associated with fibrosis progression and cirrhosis in addition to insulin resistance (IR) and inflammation. The present study was conducted to evaluate blood apelin level changes among 73 chronic hepatitis C (CHC) Egyptian patients and if associated with body mass index (BMI), IR, and tumor necrosis factor-alpha (TNF-α). Serum apelin levels were significantly higher in patients with CHC with median value (3.25) when compared with controls (1.11), at P < 0.0001, with significant apelin variations among asymptomatic carriers (ASC), fibrosis, and cirrhosis patients, and also among obese and nonobese patients. Multiple regression analysis depicted that BMI, triglycerides, and total cholesterol were independent correlation factors to apelin levels, whereas TNF-α was found to be significantly negatively correlated to adjusted apelin in CHC patients (r = −0.5944, P < 0.0001). IR was positively correlated to adjusted apelin in CHC patients (r = 0.2663, P < 0.05). Conclusion. Apelin level varies among stages of CHC, which may contribute to fibrosis progression. In addition, obesity and IR could act as comorbid factors affecting apelin level in patients with CHC

The beta secretase BACE1 regulates the expression of insulin receptor in the liver

Insulin receptor (IR) plays a key role in the control of glucose homeostasis; however, the regulation of its cellular expression remains poorly understood. Here we show that the amount of biologically active IR is regulated by the cleavage of its ectodomain, by the β-site amyloid precursor protein cleaving enzyme 1 (BACE1), in a glucose concentration-dependent manner. In vivo studies demonstrate that BACE1 regulates the amount of IR and insulin signaling in the liver. During diabetes, BACE1-dependent cleavage of IR is increased and the amount of IR in the liver is reduced, whereas infusion of a BACE1 inhibitor partially restores liver IR. We suggest the potential use of BACE1 inhibitors to enhance insulin signaling during diabetes. Additionally, we show that plasma levels of cleaved IR reflect IR isoform A expression levels in liver tumors, which prompts us to propose that the measurement of circulating cleaved IR may assist hepatic cancer detection and management

Obesity, inflammation, and insulin resistance

White adipose tissue (WAT) is considered an endocrine organ. When present in excess, WAT can influence metabolism via biologically active molecules. Following unregulated production of such molecules, adipose tissue dysfunction results, contributing to complications associated with obesity. Previous studies have implicated pro- and anti-inflammatory substances in the regulation of inflammatory response and in the development of insulin resistance. In obese individuals, pro-inflammatory molecules produced by adipose tissue contribute to the development of insulin resistance and increased risk of cardiovascular disease. On the other hand, the molecules with anti-inflammatory action, that have been associated with the improvement of insulin sensitivity, have your decreased production. Imbalance of these substances contributes significantly to metabolic disorders found in obese individuals. The current review aims to provide updated information regarding the activity of biomolecules produced by WAT

ORIGINAL ARTICLES Detection of Urinary Organic Acids in high risk Egyptian Children by Electrospray Tandem Mass Spectrometry

ABSTRACT Establishing an approach for early diagnosis and monitoring of disorders associated with accumulation organic acids in high risk Egyptian children using liquid chromatography tandem mass spectrometry (LC/MS/MS). Organic acids were detected in urine using LC/MS/MS and results were then confirmed by gas chromatography/ mass spectrometry (GC/MS). For confirmation of the type of organic acidurias (OA), acylcarnitines and/ or amino acids profiles using LC/MS/MS were done to all patients showing abnormal organic acids profiles patterns. LC/MS/MS detection of urinary organic acids revealed 31 out of 50 subjects (62%) with 11 different OAs. Organic acids profile must be done to neonates admitted to critical care units suffering unexplained neurological manifestations. The LC/MS/MS is a fast and efficient technique for the detection of many organic acids in urine and can facilitate the future screening for OA among high risk Egyptian families

Beyond mechanical loading: The metabolic contribution of obesity in osteoarthritis unveils novel therapeutic targets

Osteoarthritis (OA) is a prevalent progressive disease that frequently coexists with obesity. For several decades, OA was thought to be the result of ageing and mechanical stress on cartilage. Researchers’ perspective has been greatly transformed when cumulative findings emphasized the role of adipose tissue in the diseases. Nowadays, the metabolic effect of obesity on cartilage tissue has become an integral part of obesity research; hoping to discover a disease-modifying drug for OA. Recently, several adipokines have been reported to be associated with OA. Particularly, metrnl (meteorin-like) and retinol-binding protein 4 (RBP4) have been recognized as emerging adipokines that can mediate OA pathogenesis. Accordingly, in this review, we will summarize the latest findings concerned with the metabolic contribution of obesity in OA pathogenesis, with particular emphasis on dyslipidemia, insulin resistance and adipokines. Additionally, we will discuss the most recent adipokines that have been reported to play a role in this context. Careful consideration of these molecular mechanisms interrelated with obesity and OA will undoubtedly unveil new avenues for OA treatment

Apelin Serum Level in Egyptian Patients with Chronic Hepatitis C

Objective. Highlighting the apelin system would present a new therapeutic target for liver disease. Apelin; endogenous ligand for the orphan receptor APJ, was recently suggested to be associated with fibrosis progression and cirrhosis in addition to insulin resistance (IR) and inflammation. The present study was conducted to evaluate blood apelin level changes among 73 chronic hepatitis C (CHC) Egyptian patients and if associated with body mass index (BMI), IR, and tumor necrosis factor-alpha (TNF-α). Serum apelin levels were significantly higher in patients with CHC with median value (3.25) when compared with controls (1.11), at P<0.0001, with significant apelin variations among asymptomatic carriers (ASC), fibrosis, and cirrhosis patients, and also among obese and nonobese patients. Multiple regression analysis depicted that BMI, triglycerides, and total cholesterol were independent correlation factors to apelin levels, whereas TNF-α was found to be significantly negatively correlated to adjusted apelin in CHC patients (r=−0.5944, P<0.0001). IR was positively correlated to adjusted apelin in CHC patients (r=0.2663, P<0.05). Conclusion. Apelin level varies among stages of CHC, which may contribute to fibrosis progression. In addition, obesity and IR could act as comorbid factors affecting apelin level in patients with CHC

Pretreatment Predictors of Response to PegIFN-RBV Therapy in Egyptian Patients with HCV Genotype 4.

BACKGROUND:Egypt has the highest prevalence of a difficult to treat chronic hepatitis C virus (HCV), genotype 4. Pretreatment factors could guide individualization of therapy which aids in treatment optimization and interleukin IL28B gene polymorphism has been shown to closely relate to HCV treatment response. Polymorphisms in genes encoding inhibitors of T-cell response, which have role in disease progression as Programmed Cell Death 1 (PD-1), and Cytotoxic T-Lymphocytes Antigen-4 (CTLA-4), could be candidate markers predicting treatment response. METHODS:This cohort study consisted of 200 chronic HCV genotype 4 infected patients treated with PegIFN α-2a and RBV in 2 hepatology centers. Genotyping of the polymorphisms in the IL28B gene region (rs12979860), PD1.3 (rs11568821) and CTLA-4 (rs231775) was performed on DNA collected from each patient using TaqMan® genotyping assay. Groups were classified according to response into sustained virological responders (SVR), or non-responders (NR). A multivariate logistic regression analysis was used to identify potential markers, host pretreatment clinical and viral predictive factors including viral load, insulin resistance, and alpha fetoprotein (AFP) related to treatment response. RESULTS:Our results showed that in a multivariate analyses IL28B C/C genotype was the most significant predictor for SVR (OR = 10.86; p<0.0001) followed by AFP (OR = 0.915; p = 0.001) then CTLA-4/G genotypes (OR = 1.948; p = 0.022). However, PD-1.3/A genotypes and platelets count were significantly related to response in univariate analysis only (OR = 1.973; p = 0.023; OR = 1.007; p = 0.009 respectively). CONCLUSION:IL28B SNP, AFP level, and CTLA-4 SNP could be used in conjunction to predict treatment response in HCV genotype 4 infected Egyptian patients

Role of CTRP3, CTRP9 and MCP-1 for the evaluation of T2DM associated coronary artery disease in Egyptian postmenopausal females.

C1q complement/tumor necrosis factor (TNF)-related protein (CTRP) family comprises of 15 proteins that posses important implications in energy homeostasis, infection and inflammation. However, their roles in diabetes mellitus (DM) and its vascular complications have not been completely assessed. This works aims to study the association of two CTRPs; 3 and 9, with pro-inflammatory cytokine monocyte chemoattractant protein-1 (MCP-1), and biochemical parameters of type 2 diabetes (T2D), dyslipidemia and coronary artery disease (CAD). METHODS:Biochemical markers and serum levels of CTRPs and MCP-1 were measured in 86 postmenopausal females. Subjects were divided over four groups; 13 apparent healthy subjects as control (group I), 29 patients with CAD (group II), 29 patients with T2D ≥5 years (group III) and 15 patients with CAD secondary to T2D (group IV). Serum CTRP3, CTRP9, MCP-1 and insulin were measured by ELISA. RESULTS:Serum CTRP3 levels were found to be significantly higher in group III and IV, whereas, it was significantly lower in group II on comparing to group I. While, CTRP9 levels were significantly decreased in group II, III and IV on comparing to group I. MCP-1 levels were found to be significantly increased in groups II, III and IV on comparison with group I. Both CTRPs were significantly negatively correlated with each other. While MCP-1 was significantly correlated negatively to CTRP9. CONCLUSION:This study associates the possible role of CTRP3, CTRP9 and MCP-1/CCL2 in the diagnosis/prognosis of CAD complication in T2D postmenopausal females