Alcoholic liver disease (ALD) is a globally prevalent chronic liver disease caused by chronic or binge consumption of alcohol. The liver is the major organ that metabolizes alcohol; therefore, it is particularly sensitive to alcohol intake. Metabolites and byproducts generated during alcohol metabolism cause liver damage, leading to ALD via several mechanisms, such as impairing lipid metabolism, intensifying inflammatory reactions, and inducing fibrosis. Despite the severity of ALD, the development of novel treatments has been hampered by the lack of animal models that fully mimic human ALD. To overcome the current limitations of ALD studies and therapy development, it is necessary to understand the molecular mechanisms underlying alcohol-induced liver injury. Hence, to provide insights into the progression of ALD, this review examines previous studies conducted on alcohol metabolism in the liver. There is a particular focus on the occurrence of ALD caused by hepatotoxicity originating from alcohol metabolism.
At present, surgical treatment is the only curative option for gallbladder (GB) cancer. Many efforts therefore have been made to improve resectability and the survival rate. However, GB cancer has a low incidence, and no randomized, controlled trials have been conducted to establish the optimal treatment modalities. The present guidelines include recent recommendations based on current understanding and highlight controversial issues that require further research. For T1a GB cancer, the optimal treatment modality is simple cholecystectomy, which can be carried out as either a laparotomy or a laparoscopic surgery. For T1b GB cancer, either simple or an extended cholecystectomy is appropriate. An extended cholecystectomy is generally recommended for patients with GB cancer at stage T2 or above. In extended cholecystectomy, a wedge resection of the GB bed or a segmentectomy IVb/V can be performed and the optimal extent of lymph node dissection should include the cystic duct lymph node, the common bile duct lymph node, the lymph nodes around the hepatoduodenal ligament (the hepatic artery and portal vein lymph nodes), and the posterior superior pancreaticoduodenal lymph node. Depending on patient status and disease severity, surgeons may decide to perform palliative surgeries.Graphical Abstract
Ischemia/reperfusion injury and delayed graft function (DGF) following organ transplantation adversely affect graft function and survival. A large animal model has not been characterized. We developed a pig kidney allograft model of DGF and evaluated the cytoprotective effects of inhaled carbon monoxide (CO). We demonstrate that donor warm ischemia time is a critical determinant of DGF as evidenced by a transient (4-6 days) increase in serum creatinine and blood urea nitrogen following transplantation before returning to baseline. CO administered to recipients intraoperatively for 1 h restored kidney function more rapidly versus air-treated controls. CO reduced acute tubular necrosis, apoptosis, tissue factor expression and P-selectin expression and enhanced proliferative repair as measured by phosphorylation of retinol binding protein and histone H3. Gene microarray analyses with confirmatory PCR of biopsy specimens showed that CO blocked proinflammatory gene expression of MCP-1 and heat shock proteins. In vitro in pig renal epithelial cells, CO blocks anoxia-reoxygenation-induced cell death while promoting proliferation. This large animal model of DGF can be utilized for testing therapeutic strategies to reduce or prevent DGF in humans. The efficacy of CO on improving graft function posttransplant validates the model and offers a potentially important therapeutic strategy to improve transplant outcomes.
PurposeDespite the fact that the androgen receptor (AR) is known to be involved in the pathogenesis of breast cancer, its prognostic effect remains controversial. In this meta-analysis, we explored AR expression and its impact on survival outcomes in breast cancer.MethodsWe searched PubMed, EMBASE, Cochrane Library, ScienceDirect, SpringerLink, and Ovid databases and references of articles to identify studies reporting data until December 2013. Disease-free survival (DFS) and overall survival (OS) were analyzed by extracting the number of patients with recurrence and survival according to AR expression.ResultsThere were 16 articles that met the criteria for inclusion in our meta-analysis. DFS and OS were significantly longer in patients with AR expression compared with patients without AR expression (odds ratio [OR], 0.60; 95% confidence interval [CI], 0.40-0.90; OR, 0.53; 95% CI, 0.38-0.73, respectively). In addition, hormone receptor (HR) positive patients had a longer DFS when AR was also expressed (OR, 0.63; 95% CI, 0.41-0.98). For patients with triple negative breast cancer (TNBC), AR expression was also associated with longer DFS and OS (OR, 0.44, 95% CI, 0.26-0.75; OR, 0.26, 95% CI, 0.12-0.55, respectively). Furthermore, AR expression was associated with a longer DFS and OS in women (OR, 0.42, 95% CI, 0.27-0.64; OR, 0.47, 95% CI, 0.38-0.59, respectively). However, in men, AR expression was associated with a worse DFS (OR, 6.00; 95% CI, 1.46-24.73).ConclusionExpression of AR in breast cancer might be associated with better survival outcomes, especially in patients with HR-positive tumors and TNBC, and women. Based on this meta-analysis, we propose that AR expression might be related to prognostic features and contribute to clinical outcomes.
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