Development of Fibrosis in Nonalcoholic Steatosis through Combination of a Synthetic Diet Rich in Disaccharide and Low-Dose Lipopolysaccharides in the Livers of Zucker (fa/fa) Rats

Nonalcoholic steatohepatitis (NASH) can develop into end-stage disease such as cryptogenic cirrhosis and hepatocellular carcinoma. Hence, it is important to understand the pathogenesis of NASH. In general, the “two-hit theory” has prevailed as a pathogenic mechanism of NASH. According to this theory, lipopolysaccharides (LPS) contained in normal portal blood are the “second hit,” but their role is not completely understood. Based on this theory, we evaluated the role of LPS in NASH pathogenesis. For the first hit to develop metabolic abnormalities, a synthetic diet rich in disaccharide (synthetic diet: 12.1 cal% disaccharide) was fed to Zucker (fa/fa) rats for 12 weeks. For the second hit, 100 µg/kg LPS was injected intraperitoneally once daily for 2 weeks. Synthetic diet-fed rats treated with LPS showed an increase in the triglyceride content and higher expression of profibrogenic mRNAs in the liver. Plasma alanine aminotransferase levels were significantly elevated using this protocol. Furthermore, histological examination demonstrated that this protocol induced mild hepatic fibrosis and focal necrosis in the livers of all rats. Synthetic diet-fed Zucker (fa/fa) rats treated with LPS could be useful for understanding the development of hepatic fibrosis in the two-hit theory

Cesium Implant for Tongue Carcinoma with a Thickness of 1.5 cm or More: Cases Successfully Treated with a Modified Manchester System

∙The authors have no financial conflicts of interest. Purpose: Deciding on treatment carcinoma of the tongue when the tumor has a thickness of 1.5 cm or more is difficult. Surgery often requires wide resection and re-construction, leading to considerable functional impairment. A cesium implant is an attractive option, but according to the Manchester System, a two plane implant is needed. Materials and Methods: According to the textbook, a tumor is sandwiched between the needles, which are implanted at the edge of the tumor. This may cause an unnecessarily high dose to the outer surface of the tongue, which sometimes leads to a persistent ulcer. To avoid this complication, we invented a modified implantation method, and applied the method to five consecutive patients. Results: With a minimum follow-up of 2 years, all primary tumors in 5 consecutive patients have been controlled. No complications occurred in soft tissu

Human iPSC-derived renal collecting duct organoid model cystogenesis in ADPKD

腎集合管オルガノイドを用いた多発性嚢胞腎モデルの作製 iPS創薬により治療薬候補を発見、治験開始へ. 京都大学プレスリリース. 2023-12-01.Developing more advanced renal organoids to model polycystic kidney disease. 京都大学プレスリリース. 2023-12-01.In autosomal dominant polycystic kidney disease (ADPKD), renal cyst lesions predominantly arise from collecting ducts (CDs). However, relevant CD cyst models using human cells are lacking. Although previous reports have generated in vitro renal tubule cyst models from human induced pluripotent stem cells (hiPSCs), therapeutic drug candidates for ADPKD have not been identified. Here, by establishing expansion cultures of hiPSC-derived ureteric bud tip cells, an embryonic precursor that gives rise to CDs, we succeed in advancing the developmental stage of CD organoids and show that all CD organoids derived from PKD1−/− hiPSCs spontaneously develop multiple cysts, clarifying the initiation mechanisms of cystogenesis. Moreover, we identify retinoic acid receptor (RAR) agonists as candidate drugs that suppress in vitro cystogenesis and confirm the therapeutic effects on an ADPKD mouse model in vivo. Therefore, our in vitro CD cyst model contributes to understanding disease mechanisms and drug discovery for ADPKD

Physical properties of the Dome Fuji deep ice core (review)

Recent results of physical analyses of the Dome Fuji ice core are summarized with special attention to new methods introduced in the present studies. Microphysical processes which affect the ice core records are reviewed to better understand the paleoclimatic and paleoenvironmental signals stored

Impact of Hepatic Steatosis on Disease-Free Survival in Patients with Non-B Non-C Hepatocellular Carcinoma Undergoing Hepatic Resection.

[Background]Although the prevalence of non-B non-C hepatocellular carcinoma (NBNC HCC) has increased, its clinicopathologic characteristics remain unclear. [Methods]We retrospectively analyzed 518 HCC patients who underwent hepatic resection. Hepatitis B surface antigen- and hepatitis C antibody-negative patients were categorized into the NBNC HCC group (n = 145); others were categorized into the hepatitis B or C HCC (BC HCC) group (n = 373). We subdivided the etiologies of NBNC HCC according to alcohol intake and presence of steatosis. [Results]NBNC HCC was associated with nonalcoholic fatty liver disease (NAFLD) (13.1 %), fatty liver disease with moderate alcohol intake (9.0 %), alcoholic liver disease (ALD) (29.7 %), cryptogenic disease (44.1 %), and other known etiologies (4.1 %). The prevalence of obesity, diabetes mellitus, and hypertension was higher and hepatic function was better in the NBNC HCC group, which had significantly larger tumors than the BC HCC group. The entire NBNC HCC group displayed similar overall and disease-free survival as the BC HCC group. Among the subdivisions, NAFLD-associated HCC patients had significantly better disease-free survival than ALD-associated HCC and BC HCC patients. Microvascular invasion (hazard ratio [HR] 2.30; 95 % confidence interval [CI] 1.33–3.96) and steatosis area <5 % of noncancerous region (HR 2.13; 95 % CI 1.21–3.93) were associated with disease-free survival in NBNC HCC patients. [Conclusions]The prognosis of NBNC HCC was similar to that of BC HCC. Among NBNC HCC patients, NAFLD-associated HCC patients had a relatively low recurrence risk. Absence of steatosis in hepatic parenchyma had a significant impact on disease-free survival in NBNC HCC patients