Does Autophagy have a Role in the Pathogenesis of Pediatric Hepatic Steatosis?

Hepatic steatosis has become the most common cause of chronic liver disease among children worldwide.  Lipophagy has been considered as a pathway affecting steatosis development and progression. OBJECTIVE: this study aimed to evaluate the immunohistochemical expression of Beclin1 and LC3A in pediatric hepatic tissues with steatosis and to correlate their expression with clinicopathological parameters. METHODS: this study included 81 Egyptian pediatric patients with hepatic steatosis and 21 pediatric cases without hepatic steatosis. All specimens were stained by Beclin1 and LC3A antibodies. According to final diagnosis obtained from Pediatric Hepatology department, patients were divided into two groups: chronic liver disease (CLD) group that included 45 cases and inborn error of metabolism (IEM) group that included 36 cases. RESULTS: higher beclin1 expression was significantly correlated with higher stages of fibrosis and distorted liver architecture in CLD group, (P=0.043) for both. The control group showed higher positivity, percentage, as well as the median values of the H score of LC3A expression than did the CLD group or the IEM group (P=0.055, 0.001, and 0.008, respectively). Higher positivity of LC3A was significantly associated with higher stages of fibrosis and distorted liver architecture in the studied IEM group (P=0.021) for both. CONCLUSIONS: Varying intensity grades of LC3A and Beclin 1 immunohistochemical expression demonstrate the variation of autophagy at different phases of pediatric hepatic steatosis and varied disease etiology.

The Role of Beclin 1 and HER2 in Colorectal Carcinoma; An Immunohistochemical Study.

OBJECTIVE: This study aimed to evaluate the expression of Beclin 1 and HER2 proteins using immunohistochemistry in CRC tissues compared to colonic adenoma, and to investigate the correlation of their expression with clinicopathological parameters and survival outcomes in CRC patients. METHODS: The study utilized paraffin-embedded blocks from 17 colonic adenoma and 81 CRC cases. Immunohistochemical analysis was performed to assess the expression of Beclin 1 and HER2 proteins. RESULTS: The cytoplasmic expression of Beclin 1 was significantly higher in CRC tissues compared to adenoma specimens (P=0.051). High Beclin 1 expression was significantly associated with distal colon location (P=0.028). High HER2 cytoplasmic expression was significantly associated with vascular invasion (P=0.05), perineural invasion (P=0.03), and shorter overall survival (P=0.035). CONCLUSIONS: The findings suggest that Beclin 1 plays a role in colorectal carcinogenesis, with higher expression observed in CRC cases compared to adenoma cases.  Furthermore, HER2 carries poor prognostic impact in CRC cases.

Astaxanthin attenuates cardiovascular dysfunction associated with deoxycorticosterone acetate-salt-induced hypertension in rats.

BACKGROUND: Hypertension is a major global health problem. It is a major risk factor of cardiovascular disease. One of the most used experimental models in studying antihypertensive action is the deoxycorticosterone acetate (DOCA)-salt hypertensive rat. This study aimed to investigate the cardiovascular protective effect of astaxanthin (ASX) in DOCA-salt-induced hypertension and its possible underlying mechanisms. METHODS: A total of 48 adult male Wistar albino rats were divided into three groups: control, DOCA, and DOCA + ASX. Blood pressure, serum cardiac enzyme levels, some oxidative stress and inflammatory biomarker levels, and lipid profile levels were measured. The weight of the left ventricle to tibial length ratio was calculated. Apoptosis detection and total genomic DNA extraction in aortic and cardiac tissues were investigated. The apoptotic marker BAX was also immunohistochemically assessed in the heart and aorta. RESULTS: Compared to the control group, the DOCA group was associated with a significant increase in blood pressure, serum cardiac enzyme levels, oxidative stress and inflammatory biomarker levels, lipid profile except serum high-density lipoprotein (HDL), weight of the left ventricle to tibial length, and total released DNA fragmentation level of the left ventricle and aorta and a significant decrease in reduced glutathione (GSH) and HDL. Compared to the DOCA group, the DOCA + ASX group significantly improved the DOCA-induced changes. CONCLUSION: ASX has beneficial protective effects on DOCA-salt-induced hypertension via DNA fragmentation protection, apoptosis inhibition, antioxidant, anti-inflammatory, and its effects on lipid levels.

Role of SET oncoprotein in hepatocellular carcinoma: An immunohistochemical study.

Hepatocellular carcinoma (HCC) is the most prevalent primary cancer of the liver and it is the fourth most common cause of cancer related death worldwide. In Egypt, liver cancer constitutes the most common cause of mortality-related cancer. This study aimed to evaluate the immunohistochemical expression of SET oncoprotein in HCC tissues in comparison with its expression in non tumorous liver tissues and to correlate its expression with clinicopathological parameters. This study investigated 100 cases of HCC (including tumorous and non tumorous tissues). One hundred percent of tumorous and non-tumorous tissues were positive for SET expression. The mean and median values of H-score for SET expression were higher in tumorous than non tumorous tissues (P = .03). Higher SET expression was significantly correlated with larger tumor size (P = .012), positive lymphovascular invasion (P = .028), and shorter overall survival (P < .001). SET expression in tumor tissues is the most independent factor to affect the overall survival of HCC patients. SET plays a role in hepatocarcinogenesis proved by the increase of SET expression from non-tumorous to tumorous tissues. Also, SET can be used as a prognostic indicator and a novel target therapy in HCC patients.

Association between IFN-λ 3 Gene Polymorphisms and Outcome of Treatment with Direct Acting Antivirals in Chronic HCV-Infected Egyptian Patients.

Background: Single nucleotide polymorphisms (SNPs) of the interferon lambda 3 (IFN-λ 3) gene are associated with viral clearance and treatment response in chronic hepatitis C virus (HCV) infection. Aim: to assess whether specific IFN-λ 3 gene SNP, known as rs12979860 (C > T), could predict the outcome of treatment with direct acting antivirals (DAAs) among Egyptian patients with chronic HCV genotype 4 infection. Methods: Tetra-primer (ARMS-PCR) and PCR-RFLP methods were used for SNP genotyping in 100 chronic HCV-infected patients and 50 healthy subjects as control group. Results: The CC (wild type) genotype of rs12979860 was identified in 20 patients, 50% of them achieved sustained virological response (SVR). SNP genotype TT was found in 17 patients and only 2 of them (11.76%) were responders. The frequency of CT genotypes was significantly higher in responders than in non-responders (p= .021). In contrast, the frequency of TT genotypes was significantly higher in non-responders (42.85%, p< .001). On univariate and multivariate logistic regression analyses of the significant predictors of SVR, there were six predictive factors (Age, diabetes mellitus, AST, albumin, type of therapy and IFN-λ 3 genotype). Conclusion: The TT genotype and T allele were significantly associated with failure to achieve SVR. However, CT genotype of IFN-λ 3 (rs12979860) may be considered as a predictor for SVR in patients who received DAAs.