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CD147 is an immunoglobulin-like receptor that is highly expressed in various cancers and involved in the growth, metastasis, and activation of inflammatory pathways via interactions with various functional molecules, such as integrins, CD44, and monocarboxylate transporters. Through screening of CD147-targeting antibodies with antitumor efficacy, we discovered a novel rat monoclonal antibody # 147D. This humanized IgG4-formatted antibody, h4 # 147D, showed potent antitumor efficacy in xenograft mouse models harboring the human PDAC cell line MIA PaCa-2, HCC cell line Hep G2, and CML cell line KU812, which featured low sensitivity to the corresponding standard-of-care drugs (gemcitabine, sorafenib, and imatinib, respectively). An analysis of tumor cells derived from MIA PaCa-2 xenograft mice treated with h4 # 147D revealed that cell surface expression of CD147 and its binding partners, including CD44 and integrin α 3 β 1/ α 6 β 1, was significantly reduced by h4 # 147D. Inhibition of focal adhesion kinase (FAK), activation of multiple stress responsible signal proteins such as c-JunN-terminal kinase (JNK) and mitogen-activated protein kinase p38 (p38MAPK), and expression of SMAD4, as well as activation of caspase-3 were obviously observed in the tumor cells, suggesting that h4 # 147D induced tumor shrinkage by inducing multiple stress responsible signals. These results suggest that the anti-CD147 antibody h4 # 147D offers promise as a new antibody drug candidate., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Keisuke Fukuchi et al.)

Codeposition of Pt and Au on Ni wire was performed using a simple treatment of immersing Ni wire in aqueous solutions containing both K 2 PtCl 4 and HAuCl 4 . For evaluating the electrochemical properties of the thus-prepared electrodes, cyclic voltammograms (CVs) of 1.0 M ethanol in 1.0 M NaOH aqueous solutions were recorded. Compared with Pt- or Au-deposited Ni wire electrodes prepared by treating Ni wire in aqueous solutions of a single component, e.g., 1.0 mM K 2 PtCl 4 or 1.0 mM HAuCl 4 , a noteworthy increase in the electrocatalytic current was observed for the oxidation of ethanol with a PtAu-codeposited Ni (PtAu/Ni) wire electrode even when it was prepared in an aqueous solution containing both 0.10 mM K 2 PtCl 4 and 0.10 mM HAuCl 4 . In addition, the shape and the peak potentials of CVs recorded using PtAu/Ni wire electrodes were found to be different from those recorded with the Pt- or Au-deposited Ni wire electrodes. Because the CV responses typical of the PtAu/Ni wire electrodes were observed even when a PtAu/Ni wire electrode was prepared in an aqueous solution containing both 0.010 mM K 2 PtCl 4 and 1.0 mM HAuCl 4 , it is considered that a small amount of Pt was effectively modified or incorporated and affected the electrochemical properties significantly. The CV results for ethanol oxidation were compared with those for the electrocatalytic oxidations of methanol, 1-propanol, and 2-propanol. Besides, the CV results recorded with the present PtAu/Ni wire electrodes are discussed in comparison with some previous results obtained using other PtAu nanoelectrocatalysts., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Measurement systems are very important in urban design. This article reviews the theories of grid plans, particularly with respect to the spatial formations of ancient capital cities in Asia, and clarifies three Chinese Capital Models. The "Zhōu lǐ" Capital Model (Z) is based on the ancient text "Zhōu lǐ" that makes mention of the ideal city. However, because the description of the physical plan of the city is very brief and includes contradictory elements, conclusions regarding the specifics of the city design are extremely difficult to reach. This article proposes the most appropriate Model (Z) as an architype of the ideal Chinese city. Interestingly, there are no excavated examples of Model (Z). The two existing models, the Chang'an Capital Model (C), which is well known as the model for ancient Japanese capitals like Heiankyo (the present Kyoto) and the Dà Yuán (Dadu) Capital Model (D), the model for the city that is today Beijing, are described as Variants I and II, with a focus on the land division system of bo (street blocks).

By the selective breeding of obese male mice of the ddY strain and using indices of the heavy body weight and appearance of urinary glucose, we established two inbred strains in 1992: one with obesity and urinary glucose (Tsumura, Suzuki, Obese Diabetes: TSOD) and the other without them (Tsumura, Suzuki, Non Obesity: TSNO). The male TSOD mice constantly showed signs of obesity and urinary glucose with increases in food and water intake, body weight and some fat weight. The body mass index (BMI) clearly showed moderate obesity. Increases in the levels of diabetic blood parameters (glucose, insulin and lipids) were also found in males, in which the levels of blood glucose and insulin were high to the ages past the growth peak. In the histological studies, pancreatic islets of the TSOD males were found hypertrophic without any signs of insulitis or fibrous formation. Among these diabetic characteristics, some of which were similar to the reported models of non-insulin-dependent diabetes mellitus (NIDDM), the stable appearances of the hyperglycemia, the hyperinsulinemia and the hypertrophy of pancreatic islets to the ages past the growth peak were the prominent features. In these respect the TSOD mouse may be a useful model for researching the mechanisms of human diabetes and its complications.

The absorption and excretion of gomisin A (TJN-101) in rats whose livers were injured by carbon tetrachloride (CCl4) were investigated. After intravenous administration of TJN-101 at a dose of 5 mg/kg, the terminal elimination half-life was 1.5 h in the CCl4-treated rats, which was two times that in normal rats. The mean area under the blood concentration-time curve (AUC) value of TJN-101 in the CCl4-treated rats was twice that in normal rats, and this difference was significant (p less than 0.05). Therefore, the total body clearance of TJN-101 in the CCl4-treated rats decreased less than half of that in normal rats. Similar results were observed when it was administered orally. In the CCl4-treated rats, the serum concentration of Met. B, which was identified as a demethylenated substance and one of major metabolites, tended to decrease more than that in normal rats. On the other hand, the cumulative biliary excretion ratio of TJN-101 in 24 h after dosing in the CCl4-treated rats was 2.5 times that in normal rats. The excretion rate of Met. B in the bile in the CCl4-treated rats tended to be delayed. However, the quantitative variance of biliary excretion of Met. B was not found in both groups. The urinary excretion of TJN-101 or Met. B in 72 h after dosing in the CCl4-treated rats was lower than that in normal rats. Similar results were also observed in excretion in the feces.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of oral administration of gomisin A, one of the components isolated from Schizandra fruits, on liver injuries induced by CCl4, d-galactosamine and dl-ethionine and on liver microsomal drug-metabolizing enzyme activities were investigated. Gomisin A suppressed the increase of serum transaminase activities and the appearances of histological changes such as degeneration and necrosis of hepatocyte, inflammatory cell infiltration and fatty deposition in each type of liver injury. The repeated administration of gomisin A (30 or 100 mg/kg, p.o., daily for 4 days) induced an apparent increase of liver weight in liver-injured and normal rats. Gomisin A decreased serum triglyceride and lipid contents of the liver in biochemical studies. Increases of microsomal cytochrome b5 and P-450, elevations of NADPH cytochrome C reductase, aminopyrine N-demethylase and 7-ethoxycoumarin O-deethylase activities and decrease of 3,4-benzo(a)pyrene hydroxylase activity per cytochrome P-450 were observed after the administration of gomisin A. In addition, gomisin A was found to enhance the incorporation of 14C-phenylalanine into liver protein and to shorten the hexobarbital-induced sleeping time. These changes caused by gomisin A were similar to those by phenobarbital. However, gomisin A is distinctly different from phenobarbital in the finding that phenobarbital lessened the survival ratio of CCl4-intoxicated mice, but gomisin A did not. Our observation suggest that gomisin A shows an antihepatotoxic action by oral application and also has hypolipidemic (mainly triglyceridemic) and liver protein synthesis-facilitating actions and that the enlargement of the liver seen with gomisin A is the adaptive hypertrophy which is due to the induction of drug-metabolizing enzymes.

Some Chinese medicines in Japan have been reported to have not only antitumour effects, but also to offer protection from the adverse effects of anti-tumour agents. However, there is controversy regarding the protective effects of such Chinese medicines against the adverse effects of anti-tumour agents, in this study, we examined the effects of Tsumura Juzentaiho-to (TJ-48) on the toxicity of mitomycin C (MMC) and cisplatin (CDDP). Both the pre-administration of TJ-48 a single time and for seven days shifted the dose response curve and LD50S of MMC and CDDP to the right. Seven days of treatment using TJ-48 delayed deaths due to lethal dose of MMC or CDDP and markedly changed their survival curves. Also, TJ-48 reduced the atrophy of the testis, thymus and spleen caused by MMC. TJ-48 also had beneficial effects on leukopenia, anemia and body weight loss caused by MMC, and increase of BUN and creatinine caused by CDDP. These results indicate that the combined use of TJ-48 may be a new way to in prevent or minimize the toxicity of MMC or CDDP.

The effects of wuweizisu C, a lignan component of schizandra fruits, on liver injuries induced by carbon tetrachloride (CCl4), d-galactosamine and dl-ethionine were investigated by means of serum-biochemical and histopathological examinations in rats. Pretreatment or combined administration of wuweizisu C dose-dependently reduced the elevation of serum transaminase activity and histological changes such as fatty degeneration, cell necrosis, inflammatory cell infiltration, etc., which were caused by the single administration of 1 ml/kg, p.o., or the repeated administration of 0.2 ml/kg, s.c., daily for 4 days of CCl4, respectively. The effects of wuweizisu C on the liver injuries induced by a low dose (200 mg/kg, i.p.) and a high dose (400 mg/kg, i.p.) of d-galactosamine were compared with those of uridine. Wuweizisu C significantly lowered the rise of serum transaminase activity after the administration of a low dose of d-galactosamine in the serum-biochemical analysis. A tendency was also shown to inhibit cell necrosis and inflammatory cell infiltration caused by both doses of d-galactosamine in the histopathological examination. On the other hand, uridine markedly repaired the serum-biochemical and histopathological changes after the administrations of both doses of d-galactosamine. Also wuweizisu C cured the liver injury by the repeated administration of 150 mg/kg, i.p., daily for 4 days of d-galactosamine. After the repeated administration of 250 mg/kg, s.c., daily for 4 days of ethionine, liver cell atrophy, diffuse fatty degeneration and decrease of serum triglyceride were observed, but not cell necrosis. Wuweizisu C dose-dependently inhibited fatty degeneration and decrease of serum triglyceride. These findings suggest that wuweizisu C can be protective and/or therapeutic on hepatocellular phenomena such as cell necrosis, fatty degeneration, inflammatory cell infiltration, etc., in human hepatitis.

Effects of TJN-101, one of the components isolated from Schizandra fruits, on liver regeneration after partial hepatectomy, and on regional hepatic blood flow and fine structure of the liver were investigated in normal rats. TJN-101, which was administered orally at the doses of 10, 30 and 100 mg/kg/day for 4 days after partial hepatectomy, increased the regeneration rate of the liver and improved the serum retention rate of BSP which had been dose-dependently decreased after the operation. Elevation of serum protein to control levels, elevation of serum LCAT activity, decrease in plasma insulin and increase in plasma glucagon were all dose-dependent responses to TJN-101. The mitotic index on the 5th day after the operation was hardly influenced by TJN-101. Regional hepatic blood flow was increased after intraduodenal administration of TJN-101 (30 and 100 mg/kg). Ultrastructural studies of liver tissue using the transmission electron microscope revealed that TJN-101 stimulated an increase in rough and smooth endoplasmic reticulum in the groups receiving 100 and 300 mg/kg/day. These results suggest that TJN-101 accelerates both the proliferation of hepatocytes and the recovery of liver function after partial hepatectomy and increases hepatic blood flow. It is also thought that the liver enlargement caused by repeated administration of TJN-101 is associated with the proliferation of endoplasmic reticulum.

TJN-101 ((+)-(6S,7S,R-biar)-5,6,7,8-tetrahydro-1,2,3,12-tetramethoxy -6,7-dimethyl-10,11-methylenedioxy-6-dibenzo[a,c]cyclooctenol) is one of the lignan compounds isolated from Schisandra fruits. 1) Effect of TJN-101 on liver fibrosis was investigated in rats which were injected with CCl4 (1 ml/kg) subcutaneously twice a week for 12 weeks. TJN-101 was given orally at the dose of 10 or 30 mg/kg/day for 6 or 3 weeks beginning on the 6th or 9th week after the start of CCl4-intoxication, respectively. The elevations of serum transaminase activities and the increase of liver 4-hydroxyproline content were observed depending on the period of CCl4-intoxication. These changes were marked on the 9th and 12th weeks after. In the histopathological study, the degenerative fatty change on the 6th week after and the formation of pseudolobule caused by fibrosis proliferation on the 9th or 12th week after were mainly observed. When rats were treated with TJN-101, the abnormalities in biochemical parameters and the fibrosis proliferation caused by CCl4-intoxication were improved. 2) Chronic liver injury was induced by the treatment with CCl4 (1 ml/kg) subcutaneously twice a week for 10 weeks to investigate the effect of TJN-101 on liver regeneration after partial hepatectomy. TJN-101, which was given orally at the dose of 10, 30 or 100 mg/kg/day for 6 days from the 1st day after partial hepatectomy, dose-dependently increased the liver regeneration rate and improved the serum BSP retention rate. These results suggest that TJN-101 suppresses the fibrosis proliferation and accelerates both the liver regeneration and the recovery of liver function after partial hepatectomy in chronic liver injury.