Background: The nuclear factor E2-related factor 2-Kelch-like Ech-associated protein (NRF2-KEAP1) pathway is a major cellular defense mechanism against oxidative stress. However, the role of NRF2-KEAP1 signaling in the development of chronic liver disease remains unclear.
Methods: Clinical liver specimens from 50 hepatocellular carcinoma (HCC) developed from non-alcoholic steatohepatitis (NASH), 49 HCCs developed from chronic viral hepatitis C (CHc), and 48 liver metastases of colorectal cancer (CRC) from both tumorous and non-tumorous areas were collected during hepatic resection surgery.
Obesity is a risk factor for many diseases because it leads to a reduction in skeletal muscle mass and promotes insulin resistance. -knockout mice are a model of metabolic syndrome; show obesity, insulin resistance, and non-alcoholic fatty liver (NAFL); and develop non-alcoholic steatohepatitis (NASH) in response to the feeding of a high-fat diet (HFD). These phenotypes suggest that muscle p62 may prevent obesity-induced muscle dysfunction.
View Article and Find Full Text PDFOxidative stress (OS) contributes to nonalcoholic steatohepatitis (NASH) and hepatocarcinogenesis. We investigated whether antioxidative self-assembling nanoparticles (SMAPoTN) could reduce the development of NASH and hepatocellular carcinoma (HCC) in p62/Sqstm1 and Nrf2 double knockout (DKO) mice and studied protective mechanisms. We measured disease development in male DKO mice fed a normal chow (NASH model) or a 60% high-fat diet (HFD; HCC model) with or without SMAPoTN administration for 26 weeks.
View Article and Find Full Text PDFGender and menopause influence the severity and development manner of nonalcoholic steatohepatitis (NASH). Male p62/Sqstm1 and nuclear factor E2-related factor-2 (p62 and Nrf2) double-knockout (DKO) mice exhibit severe steatohepatitis caused by hyperphagia-induced obesity, overload of lipopolysaccharide (LPS) into the liver, and potentiation of the inflammatory response in Kupffer cells. However, the pathogenetic phenotype of steatohepatitis in female DKO mice remains unknown.
View Article and Find Full Text PDFThe standard chemotherapies for neuroendocrine tumors (NETs) are somatostatin analog (SSA) and targeted-agents for NET G1/G2 and platinum-based chemotherapy for neuroendocrine carcinoma (NEC), classified according to the WHO criteria of 2010. We report a case of NET, in which tumors were successfully treated with platinum-containing chemotherapy after remarkable progression with SSA. A 46-year-old man with multiple lymph nodes and liver metastases of unknown primary origin was diagnosed with NET G2 based on the examination of a biopsy specimen.
View Article and Find Full Text PDFBackground And Aims: We previously reported preliminary safety results for a new method, endoscopic detachable snare ligation (EDSL), for diverticular hemorrhage. This method does not need endoscope removal to attach a ligation device after detection of the bleeding site. The aim of the present study was to evaluate the efficacy and safety of EDSL in a larger patient population.
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