Ameliorative effects of zinc supplementation on cognitive function and hippocampal leptin signaling pathway in obese male and female rats.

Obesity has been associated with cognitive impairments, increasing the probability of developing dementia. Recently, zinc (Zn) supplementation has attracted an increasing attention as a therapeutic agent for cognitive disorders. Here, we investigated the potential effects of low and high doses of Zn supplementation on cognitive biomarkers and leptin signaling pathway in the hippocampus of high fat diet (HFD)-fed rats. We also explored the impact of sex difference on the response to treatment. Our results revealed a significant increase in body weight, glucose, triglycerides (TG), total cholesterol (TC), total lipids and leptin levels in obese rats as compared to controls. HFD feeding also reduced brain-derived neurotrophic factor (BDNF) levels and increased acetylcholinesterase (AChE) activity in the hippocampus of both sexes. The low and high doses of Zn supplementation improved glucose, TG, leptin, BDNF levels and AChE activity in both male and female obese rats compared to untreated ones. Additionally, downregulated expression of leptin receptor (LepR) gene and increased levels of activated signal transducer and activator of transcription 3 (p-STAT3) that observed in hippocampal tissues of obese rats were successfully normalized by both doses of Zn. In this study, the male rats were more vulnerable to HFD-induced weight gain, most of the metabolic alterations and cognition deficits than females, whereas the female obese rats were more responsive to Zn treatment. In conclusion, we suggest that Zn treatment may be effective in ameliorating obesity-related metabolic dysfunction, central leptin resistance and cognitive deficits. In addition, our findings provide evidence that males and females might differ in their response to Zn treatment.

Circulating miR-146a-5p and miR-132-3p as potential diagnostic biomarkers in epilepsy.

OBJECTIVE: MiRNAs are important gene-regulating agents in epilepsy development, according to new research. The purpose of this study is to investigate the relationship between serum expression of miR-146a-5p and miR-132-3p and epilepsy in Egyptian patients as potential diagnostic and therapeutic biomarkers. METHODS: MiR-146a-5p and miR-132-3p were measured in the serum of 40 adult epilepsy patients and 40 controls using real-time polymerase chain reaction. The comparative cycle threshold (CT) approach (2-ΔΔCT) was used to compute relative expression levels, which were normalized to cel-miR-39 expression and compared to healthy controls. The diagnostic performance of miR-146a-5p and miR-132-3p was assessed using receiver operating characteristic curve analysis. RESULTS: The relative expression levels of miR-146a-5p and miR-132-3p in serum were considerably greater in epilepsy patients than in the control group. There was a significant difference in the miRNA-146a-5p relative expression in the focal group when the non-responders were compared with the responders' groups, and a significant difference when comparing the non-responders' focal and the non-responders' generalized groups, however, univariate logistic regression analysis revealed that increased seizure frequency is the only risk factor among all factors affecting the drug response There was a significant difference in epilepsy duration between miR-132-3p high and low expression. With an area under the curve of 0.714 (95% C. I 0.598-0.830; P = 0.001), the combined miR-146a-5p and miR-132-3p serum levels performed better than each separately as a diagnostic biomarker to distinguish epilepsy patients from controls. SIGNIFICANCE: The findings imply that both miR-146a-5p and miR-132-3p may be involved in epileptogenesis regardless of epilepsy subtypes. Although the combined circulating miRNAs may be useful as a diagnostic biomarker, they are not a predictor of drug response. MiR-132-3p might be used to predict epilepsy's prognosis by demonstrating its chronicity.

Endothelial Monocyte-Activating Polypeptide-II Is an Indicator of Severity and Mortality in COVID-19 Patients.

Data for predicting the severity and mortality of coronavirus disease 2019 (COVID-19) are limited, and investigations are ongoing. Endothelial monocyte-activating protein II (EMAP-II) is a multifunctional polypeptide with pro-inflammatory properties. EMAP-II is a significant pathogenic component in chronic inflammatory lung diseases and lung injury. In this study, we aimed to assess the potential utility of EMAP-II as a predictor of COVID-19 severity and mortality. This study included 20 healthy volunteers and 60 verified COVID-19 patients. Nasopharyngeal samples from COVID-19-positive subjects and normal volunteers were collected at admission. The nasopharyngeal samples were subjected to EMAP-II real-time polymerase chain reaction (RT-PCR). EMAP-II RNA was not detected in nasopharyngeal swabs of normal controls and mild to asymptomatic COVID-19 patients and was only detectable in severe COVID-19 patients. EMAP-II critical threshold (Ct) was positively associated with lymphocyte percentages and oxygen saturation (p < 0.001) while being negatively associated with age (p = 0.041), serum CRP, ferritin, and D-dimer levels (p < 0.001). EMAP-II Ct cutoff ≤34 predicted a worse outcome in COVID-19 illness, with a sensitivity and specificity of 100%. Our study suggests that EMAP-II could be considered a potential biomarker of COVID-19 severity. EMAP-II can predict the fatal outcome in COVID-19 patients.

TGF-Β1 & PNPLA3 Genetic Variants and the Risk of Hepatic Fibrosis and HCC in Egyptian Patients with HCV-Related Liver Cirrhosis.

OBJECTIVE: The clinical outcomes of hepatitis C virus (HCV) infection and its sequelae including liver cirrhosis and hepatocellular carcinoma (HCC) are greatly affected by host genetic factors; however, the possible mechanisms are still largely unclear. This work aimed to assess transforming growth factor-ß1 (TGF-ß1), and patatin-like phospholipase domain containing-protein 3 (PNPLA3) genetic variants as risk factors for hepatic fibrosis and hepatocellular carcinoma (HCC) in Egyptian patients with HCV-related liver cirrhosis. METHODS: Seventy HCV-related liver cirrhosis patients (Total cirrhosis) who were divided into two groups; 34 patients with HCC (HCC group), and 36 patients without HCC (LC group) and 20 healthy volunteers (control group) were included. Routine laboratory investigations and imaging studies were determined. TGF-ß1 (Arg25Pro; 915G>C) and PNPLA3 (I148M; C>G) variants were evaluated using real-time polymerase chain reaction (real-time PCR). RESULTS: HCC group showed a significantly higher GG genotype distribution of TGF-ß1 (Arg25Pro) than the LC group (P= 0.008, OR: 7.083, CI 95%: 1.422 - 35.282). The distributions of GG genotype (P= 0.047) and G allele (P= 0.002, OR: 4.395, CI 95%: 1.622 - 11.911) of PNPLA3 (I148M) were significantly higher in total cirrhosis patients than controls. CONCLUSION: TGF-ß1 (Arg25Pro) GG variant may be associated with HCC risk in HCV-related liver cirrhosis patients, while PNPLA3 (I148M) GG variant may be associated with cirrhosis development but not HCC risk in HCV-related liver cirrhosis patients.

The clinical significance of serum miRNA-224 expression in hepatocellular carcinoma.

AIM OF THE STUDY: Micro-ribonucleic acids (miRNA) are small single stranded RNA molecules. They act as key regulators of several cellular processes such as proliferation, apoptosis, tumor differentiation, invasion and metastasis. Hepatocellular carcinoma (HCC) represents the most common primary liver cancer. miRNA-224 is an oncomiR that is highly upregulated in HCC tissues. The aim of the present study was to measure the relative expression of circulating miRNA-224 in the serum of patients with HCV-related liver cirrhosis and HCC and to assess its usefulness in the diagnosis of HCC. MATERIAL AND METHODS: Forty-eight patients were classified into two groups: 24 HCV-related HCC patients (HCC group), and 24 HCV-related liver cirrhosis patients (LC group). A third group included 24 healthy volunteers (control group). Clinical examination, imaging studies and routine laboratory investigations, including serum α-fetoprotein (AFP), were done. Quantification of serum miRNA-224 expression was performed using real time reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The relative expression of serum miRNA-224 was significantly higher in HCC patients compared to LC patients and healthy control subjects. Its level correlated positively with the serum concentration of AFP and with Barcelona Clinic Liver Cancer (BCLC) stage of HCC. By combining miRNA-224 relative expression with AFP, their diagnostic sensitivity, specificity and accuracy increased significantly (95.0%, 92.1% and 93.2%, respectively) compared with either of the two markers alone in discriminating HCC from liver cirrhosis. CONCLUSIONS: Serum miRNA-224 relative expression may aid in the diagnosis of HCC. Better diagnostic performance is obtained if miRNA-224 is combined with other tumor markers such as AFP.

Profiling of plasma metabolomics in patients with hepatitis C-related liver cirrhosis and hepatocellular carcinoma.

AIM OF THE STUDY: The diagnosis of hepatocellular carcinoma (HCC) is usually late, due to the lack of early detection of biomarkers for HCC. Metabolomics analysis has emerged as a useful tool for studying human diseases. The objective of the study was to investigate the differences in plasma metabolites between hepatitis C virus (HCV)-induced cirrhosis and HCC. MATERIAL AND METHODS: 22 subjects with HCV-related liver cirrhosis and 22 subjects with HCC were enrolled. Clinical, routine laboratory and imaging studies were done. Gas chromatography/mass spectrometry (GC/MS) was used for metabolomics analysis of patients' plasma samples. RESULTS: 34 known metabolites were detected, of which five metabolites were identified to have the strongest discriminatory power for separation between HCC and cirrhosis groups: octanoic acid (caprylic acid), decanoic (capric acid), oleic acid, oxalic acid and glycine. These are 3 fatty acids (FA), a dicarboxylic acid and a glucogenic amino acid, respectively. No significant correlation was found between the relative intensities of the five metabolites and any of the patient or tumor characteristics (Child-Turcotte-Pugh (CTP) score, Barcelona Clinic Liver Cancer (BCLC) stage, number of focal lesions and size of largest focal lesion). ROC curve analysis was performed and area under the curve (AUC) was calculated, revealing that oleic acid, octanoic (caprylic) acid and glycine had higher positive predictive value than α-fetoprotein. CONCLUSIONS: The study of metabolomics (particularly involving FA) may help define distinct metabolic patterns to distinguish HCV-induced liver cirrhosis from HCC patients. Future research in this field is still needed, particularly concerning HCC treatment strategies which target fatty acid-related metabolic pathways.

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.