A 55-year-old man treated with dialysis due to diabetic nephropathy developed acute abdominal pain and was brought to our hospital by ambulance. The patient was initially under observation because the symptoms were mild and enhanced computed tomography revealed no remarkable findings. However, a laparotomy was performed after 24 hours because laboratory findings indicative of inflammation were enhanced, and the abdominal pain did not improve. The laparotomy revealed discontinuous segmental intestinal ischemia, and the patient was diagnosed with non-occlusive mesenteric ischemia. A continuous intravenous infusion (0.01 μg/kg/min) of prostaglandin E1 (PGE1) was started, and the necrotic small intestine and ascending and transverse colon were resected and anastomosed. Two days after surgery, anastomotic leak due to intestinal ischemia was suggested, and a second laparotomy was performed. The intestinal ischemic changes had worsened. Therefore, additional intestine was resected, an ileostomy was performed, and the PGE1 dose was increased to 0.05 μg/kg/min. After the second surgery, the patient's general condition and intestinal ischemia improved, and the color of the ileostomy was good. However, 42 days after the second surgery, the diabetic patient died from sepsis. Thus, the continuous intravenous infusion of PGE1 and the appropriately timed resection of necrotizing bowel are necessary for treatment of non-occlusive mesenteric ischemia, and the concurrent management of pre-existing disease should not be forgotten.

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The retina has a well-organized cellular structure and belongs to the central nervous system. The retina has been used as a model of the central nervous system, especially neuronal degeneration and axonal regeneration. Monoclonal C38 antibody has been used as a molecular marker of retinal ganglion cells, but the molecular function of its antigen has not been clarified. A recent study has demonstrated that C38 is a neuron-specific mitochondrial protein that enhances neuronal maturation. This review outlines the functions of C38, as investigated through a retina model.

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Chronic hepatitis B virus (HBV) infection is the most major risk factor for the development of hepatocellular carcinoma (HCC) worldwide. After decades of chronic hepatitis, about 30–40% of patient progress into liver cirrhosis, and of them, around 1–5% subsequently develops HCC annually. However, some HCC with HBV infection occur on livers with minimal histological changes or in young adult, which is HBV itself may contribute to carcinogenesis. Hepatitis B virus X protein (HBx) is suspected to participate in oncogenesis during chronic hepatitis B progression. Although HBx does not bind DNA directly, HBx activates Ras/mitogen-activated protein kinase (MAPK) pathways such as p38, Erk and c-Jun N-terminal kinase (JNK), resulting in uncontrolled proliferation and invasion of hepatic tumor cells.
Transforming growth factor beta (TGF-β) has a complex role in HCC. TGF-β signaling involves both tumor suppression and oncogenesis; A bipartite role has been seen to TGF-β, which has tumor suppressor function at early stages of liver damage, while TGF-β switch from being a tumor suppressor into being a tumor promoter that induced invasive and metastatic behavior at carcinogenic stages. TGF-β activates TGF-β type I receptor (TβRI) and c-Jun N-terminal kinase (JNK), which convert the mediator Smad3 into two distinctive phosphoisoforms: C-terminally phosphorylated Smad3 (pSmad3C) and linker-phosphorylated Smad3 (pSmad3L).
By immunostaining, immunoblotting, and in vitro kinase assay, we compared pSmad3L- and pSmad3C-mediated signaling in biopsy specimens representing chronic hepatitis, cirrhosis, or hepatocellular carcinoma (HCC) from 90 patients chronically infected by hepatitis B virus (HBV) with signaling in HBx transgenic mice. We also correlated patient's Smad3 phosphorylation with their clinical course.
In proportion to plasma HBV-DNA levels, but irrespective of necroinflammatory activity, chronic hepatitis B specimens showed prominence of JNK-dependent pSmad3L in hepatocytic nuclei. In both HBx transgenic mouse liver and chronic hepatitis B liver, oncogenic pSmad3L pathway in hepatocytes came to predominate while the tumor-suppressive pSmad3C pathway became quiescent as liver damage progressed to HCC. HCC developed in 6 of 28 patients with high Smad3L phosphorylation, but in only 1 of 32 patients with low Smad3L phosphorylation (log-rank = 0.03). In contrast, HCC developed only in the patients with low Smad3C phosphorylation, and no patients with high hepatocytic pSmad3C developed HCC (log-rank = 0.009).
This report will focus on phosphorylation of Smad3 and summarize our current knowledge on TGF-β signaling involved in HBV-related hepatocarcinogenesis, leading to create molecular targets for future therapy.

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