RESUMO
Liver ischemia-reperfusion injury (IRI) is a pathophysiological insult that often occurs during liver surgery. Blackberry leaves are known for their anti-inflammatory and antioxidant activities. AIMS: To achieve site-specific delivery of blackberry leaves extract (BBE) loaded AgNPs to the hepatocyte in IRI and to verify possible molecular mechanisms. METHODS: IRI was induced in male Wister rats. Liver injury, hepatic histology, oxidative stress markers, hepatic expression of apoptosis-related proteins were evaluated. Non-targeted metabolomics for chemical characterization of blackberry leaves extract was performed. KEY FINDINGS: Pre-treatment with BBE protected against the deterioration caused by I/R, depicted by a significant improvement of liver functions and structure, as well as reduction of oxidative stress with a concomitant increase in antioxidants. Additionally, BBE promoted phosphorylation of antiapoptotic proteins; PI3K, Akt and mTOR, while apoptotic proteins; Bax, Casp-9 and cleaved Casp-3 expressions were decreased. LC-HRMS-based metabolomics identified a range of metabolites, mainly flavonoids and anthocyanins. Upon comprehensive virtual screening and molecular dynamics simulation, the major annotated anthocyanins, cyanidin and pelargonidin glucosides, were suggested to act as PLA2 inhibitors. SIGNIFICANCE: BBE can ameliorate hepatic IRI augmented by BBE-AgNPs nano-formulation via suppressing, oxidative stress and apoptosis as well as stimulation of PI3K/Akt/mTOR signaling pathway.
RESUMO
Viral hepatitis B (HBV) and hepatitis C (HCV) infections remain the most common risk factors for the development of hepatocellular carcinoma (HCC), and their heterogeneous distribution influences the global prevalence of this common type of liver cancer. Typical hepatitis infection elicits various immune responses within the liver microenvironment, and viral persistence induces chronic liver inflammation and carcinogenesis. HBV is directly mutagenic but can also cause low-grade liver inflammation characterized by episodes of intermittent high-grade liver inflammation, liver fibrosis, and cirrhosis, which can progress to decompensated liver disease and HCC. Equally, the absence of key innate and adaptive immune responses in chronic HCV infection dampens viral eradication and induces an exhausted and immunosuppressive liver niche that favors HCC development and progression. The objectives of this review are to (i) discuss the epidemiological pattern of HBV and HCV infections, (ii) understand the host immune response to acute and chronic viral hepatitis, and (iii) explore the link between this diseased immune environment and the development and progression of HCC in preclinical models and HCC patients.
RESUMO
PURPOSE: Debate exists for the optimal tool to select embryos for transfer in assisted reproductive technology (ART). Time-lapse monitoring (TLM) is a noninvasive tool suggested where each embryo can be captured every 5-20 min. Given the inconsistency in the existing studies, we conducted this meta-analysis of RCTs to summarize the evidence available concerning the predictive ability of morphokinetics compared with the routine assessment of embryo development in ART. METHODS: The primary databases MEDLINE, EMBASE, Cochrane, NHS, WHO, and Other Non-Indexed Citations were consulted for RCTs that have been published until November 2018, with no language restriction. RESULTS AND CONCLUSION: Our review includes 6 RCTs (n = 2057 patients). The data showed an improvement (~ 9%) in live birth TLM (OR 1.43; 95% CI 1.10-1.85; P = 0.007), with low-quality evidence. There was no evidence of a significant difference between both groups concerning ongoing pregnancy, clinical pregnancy and implantation rates. The data further showed that morphokinetics is associated with decreased early pregnancy loss rate. These estimates must be interpreted with caution owing to the statistical and clinical heterogeneities and the consequent difficulty in drawing any meaningful conclusion.