Hyperglycemia in the diabetic state increases oxidative stress and antioxidant therapy can be strongly correlated with decreased risks for diabetic complications. The purpose of this study is to ...determine antioxidant effect of garlic and aged black garlic in animal model of type 2 diabetes. The antioxidant activity of garlic and aged black garlic was measured as the activity in scavenging free radicals by the trolox equivalent antioxidant capacity (TEAC) assay. Three week-old db/db mice were fed AIN-93G diet or diet containing 5% freeze-dried garlic or aged black garlic for 7 weeks after 1 week of adaptation. Hepatic levels of lipid peroxides and activities of antioxidant enzymes were measured. TEAC values of garlic and aged black garlic were 13.3 ± 0.5 and 59.2 ± 0.8 μmol/g wet weight, respectively. Consumption of aged black garlic significantly decreased hepatic thiobarbituric acid reactive substances (TBARS) level compared with the garlic group which showed lower TBARS level than control group (p less than 0.05). Activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) of garlic and aged black garlic group were significantly elevated compared to the control group. Catalase (CAT) activity of aged black garlic group was increased compared with the control group. These results show that aged black garlic exerts stronger antioxidant activity than garlic in vitro and in vivo, suggesting garlic and aged black garlic, to a greater extent, could be useful in preventing diabetic complications.
Evasive shareholder meetings and corporate fraud Gam, Yong Kyu; Gupta, Paramita; Im, Jieun ...
Journal of corporate finance (Amsterdam, Netherlands),
February 2021, 2021-02-00, Letnik:
66
Journal Article
Recenzirano
We examine how evasive shareholder meetings are related to the likelihood of committing corporate fraud. In this study, we use changes in corporate policy to hold an AGM on certain popular dates as a ...proxy for evasive management practices. We find that the positive implications of strategic AGM scheduling for committing corporate fraud are greater for firms that hold their AGM away from headquarters, firms managed by professional CEOs, and firms whose AGM agendas include audit election or dismissal. The positive correlations are, however, less likely when evasive practices are spread throughout the same industry.
•Show positive link between evasive corporate governance and corporate fraud.•Use changes in corporate policy to hold an AGM on certain popular dates as a proxy for evasive management practices.•Highlight the case of South Korea where shareholders likely serve as an additional monitor of financial reports.
Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis due to the absence of diagnostic markers and molecular targets. Here, we took an unconventional approach to identify new molecular ...targets for pancreatic cancer. We chose uncharacterized protein evidence level 1 without function annotation from extensive proteomic research on pancreatic cancer and focused on proline and serine-rich 2 (PROSER2), which ranked high in the cell membrane and cytoplasm. In our study using cell lines and patient-derived orthotopic xenograft cells, PROSER2 exhibited a higher expression in cells derived from primary tumors than in those from metastatic tissues. PROSER2 was localized in the cell membrane and cytosol by immunocytochemistry. PROSER2 overexpression significantly reduced the metastatic ability of cancer cells, whereas its suppression had the opposite effect. Proteomic analysis revealed that PROSER2 interacts with STK25 and PDCD10, and their binding was confirmed by immunoprecipitation and immunocytochemistry. STK25 knockdown enhanced metastasis by decreasing p-AMPK levels, whereas PROSER2-overexpressing cells increased the level of p-AMPK, indicating that PROSER2 suppresses invasion via the AMPK pathway by interacting with STK25. This is the first demonstration of the novel role of PROSER2 in antagonizing tumor progression via the STK25-AMPK pathway in PDAC. LC–MS/MS data are available at MassIVE (MSV000092953) and ProteomeXchange (PXD045646).
Control of hyperglycemia and dyslipidemia is strongly correlated with decreased risk for cardiovascular disease, the most common and fatal diabetic complication. The purpose of this study is to ...determine the effects of garlic and aged black garlic on glycemic control and blood lipid profile in animal model of type 2 diabetes. Three week-old db/db mice (C57BL/Ks, n=21) were fed AIN-93G semipurified diet or diet containing 5% freeze-dried garlic or aged black garlic for 7 weeks after 1 week of adaptation. Fasting serum glucose, insulin, triglyceride, total cholesterol, and HDL-cholesterol and blood glycated hemoglobin were measured. Body weight and food intake of garlic and aged black garlic group were not significantly different from those of the control group. Fasting serum glucose and blood glycated hemoglobin levels were significantly decreased and insulin level was significantly increased in garlic group compared with control group (p<0.05). Consumption of aged black garlic significantly decreased homeostasis model assessment for insulin resistance (HOMA-IR) and tended to decrease serum glucose. Garlic consumption significantly decreased total cholesterol, while aged black garlic significantly reduced serum total cholesterol and triglyceride and increased HDL-cholesterol levels. These results suggest that garlic exerts hypoglycemic and hypocholesterolemic effect and aged black garlic improved insulin sensitivity and dyslipidemia in db/db mice. KCI Citation Count: 6
The present study examined the effect of the king oyster mushroom (Pleurotus eryngii) on insulin resistance and dyslipidemia in db/db mice. Four-week-old db/db mice were fed an AIN-93G diet or a diet ...containing 5% king oyster mushroom for 7 weeks. The blood glycated hemoglobin and serum glucose levels in the mushroom group were significantly. lower than the control group (p less than 0.05). Dietary king oyster mushroom significantly reduced the homeostasis model assessment for insulin resistance (HOMA-IR), total cholesterol, and triglyceride, and increased high density lipoprotein (HDL)-cholesterol. These results indicate that king oyster mushroom improves insulin sensitivity and exerts anti-hyperglycemic and anti-hyperlipidemic effects in db/db mice.
Abstract
FAM20C reported as a novel secreted kinase has the potential of phosphorylation on consensus motif, S-x-E/pS, of secretory proteins or ectodomain of membrane proteins. Numerous substrate ...candidates through prediction implied FAM20C has the function on tumor microenvironment, however, function and regulatory mechanism of cancer progression by FAM20C has not been defined yet. As tumor associated macrophage (TAM) changes to have the tumor supporting phenotype in response to various environmental stimuli, TAM is the potent regulatory target of FAM20C in tumor microenvironment. In this study, we hypothesized that the secreted kinase FAM20C in tumor microenvironment can support pancreatic cancer progression by regulating TAM contents or polarization. In pancreatic orthotopic xenograft model of FAM20C-overexpressing tumor cells, the tumor growth rate was enhanced and TAM contents (F4/80+/CD11b+/MHCII+) were significantly increased compared to control group, while total macrophage population between two groups had no difference. Moreover, the high level of TAM contents was sustained in the presence of FAM20C till the late stage of tumor progression. In addition, infiltrated tissue macrophages were polarized into TAM by FAM20C treatment Furthermore, increased TAM population by FAM20C suppresses the CD8+ cytotoxic T cell proliferation with anti-tumor function. Collectively, FAM20C might be a key regulatory factor in pancreatic cancer progression by promoting polarization of TAM.
Citation Format: Jieun Im, Yu-Sun Lee, Sun Il Choi, Beom-Kyu Choi, A-Ra Jeon, Sang Hyun Park, Min-Kyeong Lee, Joon-Ki Kim, Yun-Hee Kim. Key role of secreted kinase FAM20C on tumor associated macrophage (TAM) leading to pancreatic cancer progression abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3138.
Amphiphilic cyclodextrins have been synthesized with self-acylating reaction using vinyl esters in dimethylformamide. In the present study no base, catalyst, or enzyme was used, and the structural ...analyses using thin layer chromatography, nuclear magnetic resonance spectroscopy and mass spectrometry show that the cyclodextrin is substituted preferentially by one acyl moiety at the C2 position of the glucose unit, suggesting that cyclodextrin functions as a regioselective catalytic carbohydrate in organic solvent. In the self-acylation, the most acidic OH group at the 2-position and the inclusion complexing ability of cyclodextrin were considered to be significant. The substrate preference was also observed in favor of the long-chain acyl group, which could be attributed to the inclusion ability of cyclodextrin cavity. Furthermore, using the model amphiphilic building block, 2-O-mono-lauryl β-cyclodextrin, the self-organized supramolecular architecture with nano-vesicular morphology in water was investigated by fluorescence spectroscopy, dynamic light scattering and transmission electron microscopy. The cavity-type nano-assembled vesicle and the novel synthetic methods for the preparation of mono-acylated cyclodextrin should be of great interest with regard to drug/gene delivery systems, functional surfactants, and carbohydrate derivatization methods.
Abstract Background Live biotherapeutic products (LBPs) are known to enhance immune responses through the GUT-TME axis. Here, we investigate the GUT-TME-related immune cell profiling and signals ...associated with the anti-cancer effects of CJRB-101. Methods Tumors from NSCLC patients (anti-PD-1 refractory) were transplanted in Hu-CD34-NSG to establish humanized patient-derived xenograft (PDX) models. CJRB-101 was administered at 1x109 CFU (p.o., BID) or combination with anti-PD-1 (10 mpk, i.p., BIW). TME was analyzed using multiplex IHC, flow cytometry and scRNA sequencing. Samples were collected from C3PQ syngeneic mice at multiple timepoints for GUT-TME immune cell profiling. For depletion assay, immune cells were individually depleted during the combination treatment. TLR4-mediated mechanism was evaluated using ex vivo and in vivo assay treated with CJRB-101 or cell membrane of CJRB-101. Results CJRB-101 combined with pembrolizumab effectively suppressed tumor growth in anti-PD-1 resistant PDX models. Further analysis revealed a correlation between the activity of NK cells and angiogenesis inhibition. Abundance of NK/NKT was higher in the CJRB-101 treated group compared to the vehicle group in multiple PDX models. The expression of GZMB and IFNG in NK/NKT cells was significantly higher in the CJRB-101 treated group compared to the vehicle group in YHIM2014 (p<0.001). CJRB-101 treated group showed significantly higher expression of antiangiogenic IL1B (p<0.001) while the expression of pro-angiogenic VEGFA (p=0.002) was lower compared to the vehicle group in YHIM2014 cancer cells. Macrophages in the intestine were increased at Day 3 in the CJRB-101 group compared to anti-PD1, while NK cells, granulocytes, CD3+, CD4+, CD8+ T cells increased at Day 10 in the syngeneic model. Depletion assay confirmed that macrophages, CD8+ T cells and neutrophils were pivotal in the anti-cancer effects of CJRB-101. We observed that TAK242 and MD2 reduced the IL-6 secretion of Raw264.7 in a dose-dependent manner. The cell membrane played a key role in increasing BMDM M1 polarization and repolarization of M2 to M1, and that inhibition of TLR4 resulted in a decrease in BMDM repolarization. TLR inhibition also demonstrated that TGI decreased from 34% to 20% when treated with cell membrane + TAK242 compared to cell membrane monotherapy. Conclusions This study showed that macrophages were the dominant immune population in the early stages then T cells (CD3, CD4, CD8), NK cells and granulocytes became more active in the latter stages of the GUT-TME-axis immune response. In vivo results indicated that anti-cancer efficacy of CJRB-101 is immune-cell driven by TLR4-dependent stimulation of key immune cell populations (macrophages, CD8+ T cells, neutrophils) modulated by the cell membrane of CJRB-101. CJRB-101 is currently undergoing clinical investigation for treatment of patients with advanced NSCLC. Citation Format: Arim Min, Bo-eun Kwon, Seong-san Kang, Sujeong Baek, Junwon Yang, Hyunkyung Park, Jieun Im, Hyunjeong Kim, Jaemin Kim, Jieun Kwon, Dong Kwon Kim, Jii Bum Lee, Hyeonseok Oh, Seung Min Yang, Yu Jin Han, Mi hyun Kim, Heekyung Han, Kwangmin Na, Young Taek Kim, Mi Ran Yun, Jae Hwan Kim, Youngseon Byeon, Young Seob Kim, Min Hee Hong, Sun Min Lim, Kyoung-Ho Pyo, Byoung Chul Cho. CJRB-101 induces immune responses through the GUT-TME axis in immune cell-driven mechanism in lung cancer models abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4993.
Abstract
To develop an efficient drug screening platform which overcomes the difference of drug response between initial screening and clinical trial stage is a pivotal issue for drug discovery. The ...patient-derived Xenograft (PDX) model has been reported as a screening system to reflect the microenvironment and heterogeneity of tumor. However, in pancreatic cancer that 80 % of patients is non-resectable, PDX is not be suitable for an initial screening model in terms of economic- and time cost of mouse-based amplification system as well as the lack of obtaining pancreatic tumor tissue from fine needle biopsy or percutaneous gun. To overcome this limitation, here we newly suggested organoids system, miniature organ culture on a dish, that are generated from tumor tissues of orthotopic PDX model, which has the advantages of reflection of each patient's characteristics as well as amplification of limited tumor tissue. Besides, it is possible to screen of drug responsibility with a little number of cells. 12 organoids derived from PDX using needle or gun biopsy tumor tissues showed EpCAM overexpression and each unique morphological phenotype. Moreover, from drug responsibility test, H #43 and H #44, an organoids derived from a gemcitabine-sensitive patients, were highly responsible to gemcitabine, whereas the organoids from gemcitabine-resistant patients, G #20 and H #19 showed a strong resistance to gemcitabine as measuring the IC50 value. In addition, combined treatment with gemcitabine and abraxane to the G #13 model which has no clinical information of drug response due to early death, it inhibited organoid formation significantly, showing a combination index below 1, which was proved through in vivo (PDX) validation. Taken together, the PDX-Organoid system might be able to reflect primary tumor characteristics as well as to overcome the quantitative limitations of the specimen and time cost, and thereby it is possible to predict drug response early in vitro, making it very efficient as an anti-cancer drug development platform for pancreatic cancer.
Citation Format: A-Ra Jeon, Sun Il Choi, Sang-Jae Park, Sung-Sik Han, Sun-Young Kong, Min Kyeong Kim, Yu-sun Lee, Jieun Im, Min Kyeong Lee, Sang Hyun Park, Joon-Ki Kim, Kyong-Ah Yoon, Young-Hwan Koh, Ju Hee Lee, Woo Jin Lee, Sang Myung Woo, Yun-Hee Kim. New strategy of drug response assessment using PDX organoid platform for non-resectable pancreatic cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4098.
This study examines how treasury shares held by Korea’s publicly traded firms may affect firm value. Unlike in the U.S., where repurchased shares are immediately subtracted from market ...capitalization, and thus, constitute a genuine payout mechanism, Korean stock market practice retains the value of repurchased shares in market capitalization, effectively treating treasury shares as a form of an asset. Korean investors do not consider share repurchase as a payout mechanism until the repurchased shares are formally cancelled. We find that share repurchases are followed by positive market reactions, which is consistent with the results of previous research, but the reactions are even larger on the cancellation disclosure date. More importantly, firms with larger treasury shares in stock exhibit a 24% lower Tobin’s q compared to those firms with smaller treasury shares. These findings suggest that the market anticipates that treasury shares may be used as a potential antitakeover measure at a later date, which is reflected in the current market value.
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