• 제목/요약/키워드: Hepatic cells

검색결과 649건 처리시간 0.026초

Investigation of the efficacy of mycotoxin-detoxifying additive on health and growth of newly-weaned pigs under deoxynivalenol challenges

  • Holanda, Debora Muratori;Kim, Sung Woo
    • Animal Bioscience
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    • 제34권3_spc호
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    • pp.405-416
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    • 2021
  • Objective: This study evaluated the effects of feeding diets naturally contaminated with deoxynivalenol (supplemental 2 mg/kg) on health, growth, and the effects of a mycotoxin-detoxifying additive in newly-weaned pigs. Methods: Thirty-six pigs (27 day-old) were housed individually and assigned to 3 treatments for 5 weeks: CON (diet containing minimal deoxynivalenol), MT (diet with supplemental 1.9 mg/kg of deoxynivalenol), and MT+D (MT + mycotoxin-detoxifying additive, 0.2%, MegaFix, ICC, São Paulo, Brazil). The mycotoxin-detoxifying additive included bentonite, algae, enzymes, and yeast. Blood was taken at week 2 and 5. Jejunal tissue were taken at week 5. Data were analyzed using the MIXED procedure of SAS. Results: Pigs fed MT+D tended to have decreased (p = 0.056) averaged daily feed intake during week 1 than MT. At week 2, serum aspartate aminotransferase/alanine aminotransferase in MT tended to be lower (p = 0.059) than CON, whereas it was increased (p<0.05) for MT+D than MT, indicating hepatic damages in MT and recovery in MT+D. Pigs fed MT had lower (p<0.05) blood urea nitrogen/creatinine than CON, supporting hepatic damage. At week 5, pigs fed MT tended to have reduced (p = 0.079) glucose than CON, whereas it was increased (p<0.05) for MT+D than MT, indicating impaired intestinal glucose absorption in MT, which was improved in MT+D. Pigs fed CON tended to have increased (p = 0.057) total glutathione in jejunum than MT, indicating oxidative stress in MT. Pigs fed MT+D had a reduced (p<0.05) proportion of Ki-67-positive cells in jejunum than MT, indicating lower enterocyte proliferation in MT+D. Conclusion: Feeding supplemental 1.9 mg/kg of deoxynivalenol reduced growth and debilitated hepatic health of pigs, as seen in leakage of hepatic enzymes, impaired nitrogen metabolism, and increase in oxidative stress. The mycotoxin-detoxifying enhanced hepatic health and glucose levels, and attenuated gut damage in pigs fed deoxynivalenol contaminated diets.

Loss of hepatic Sirt7 accelerates diethylnitrosamine (DEN)-induced formation of hepatocellular carcinoma by impairing DNA damage repair

  • Yuna Kim;Baeki E. Kang;Karim Gariani;Joanna Gariani;Junguee Lee;Hyun-Jin Kim;Chang-Woo Lee;Kristina Schoonjans;Johan Auwerx;Dongryeol Ryu
    • BMB Reports
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    • 제57권2호
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    • pp.98-103
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    • 2024
  • The mammalian sirtuin family (SIRT1-SIRT7) has shown diverse biological roles in the regulation and maintenance of genome stability under genotoxic stress. SIRT7, one of the least studied sirtuin, has been demonstrated to be a key factor for DNA damage response (DDR). However, conflicting results have proposed that Sirt7 is an oncogenic factor to promote transformation in cancer cells. To address this inconsistency, we investigated properties of SIRT7 in hepatocellular carcinoma (HCC) regulation under DNA damage and found that loss of hepatic Sirt7 accelerated HCC progression. Specifically, the number, size, and volume of hepatic tumor colonies in diethylnitrosamine (DEN) injected Sirt7-deficient liver were markedly enhanced. Further, levels of HCC progression markers and pro-inflammatory cytokines were significantly elevated in the absence of hepatic Sirt7, unlike those in the control. In chromatin, SIRT7 was stabilized and colocalized to damage site by inhibiting the induction of γH2AX under DNA damage. Together, our findings suggest that SIRT7 is a crucial factor for DNA damage repair and that hepatic loss-of-Sirt7 can promote genomic instability and accelerate HCC development, unlike early studies describing that Sirt7 is an oncogenic factor.

DA-6034 ameliorates hepatic steatosis and inflammation in high fat diet-induced obese mice

  • Hong Min Kim;Mi-Hye Kwon;Eun Soo Lee;Kyung Bong Ha;Choon Hee Chung
    • Journal of Yeungnam Medical Science
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    • 제41권2호
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    • pp.103-112
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    • 2024
  • Background: Nonalcoholic fatty liver disease (NAFLD) is characterized by an increase in hepatic triglyceride content and increased inflammatory macrophage infiltration through the C-C motif chemokine receptor (CCR) 5 pathway in the liver. DA-6034 (7-carboxymethyloxy-3',4',5-trimethoxy flavone), is a synthetic derivative of eupatilin that exhibits anti-inflammatory activity in inflammatory bowel disease. However, the effect of DA-6034 on the inflammatory response in NAFLD is not well elucidated. Therefore, we aimed to determine the effect of DA-6034 on hepatic steatosis and inflammation. Methods: Forty male C57BL/6J mice were divided into the following four groups: (1) regular diet (RD), (2) RD with DA-6034, (3) high fat diet (HFD), and (4) HFD with DA-6034. All mice were sacrificed 12 weeks after the start of the experiment. The effects of DA-6034 on macrophages were assessed using RAW 264.7 cells. Results: DA-6034 not only reduced hepatic triglyceride levels and lipid accumulation but also macrophage infiltration and proinflammatory cytokines in HFD-fed mice. According to fluorescence-activated cell sorter analysis, DA-6034 reduced the CD8+ T cell fraction in the liver of HFD-fed mice. DA-6034 also reduced CCR5 expression and the migration of liver macrophages in HFD-fed mice and inhibited CCR2 ligand and CCR4 ligand, which stimulated the migration of macrophages. Conclusion: Overall, DA-6034 attenuates hepatic steatosis and inflammation in obesity by regulating CCR5 expression in macrophages.

위암의 재발양상에 따른 혈관내피성장인자의 발현 (Expression of Vascular Endothelial Growth Factor Correlated with Recurrence in Gastric Carcinomas)

  • 성기영;박일영;이도상;김욱;백종민;신동준;원종만;이재학
    • Journal of Gastric Cancer
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    • 제2권4호
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    • pp.195-199
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    • 2002
  • Purpose: Angiogenesis is essential for tumor growth and metastasis and depends on the production of angiogenic factors that are secreted by tumor cells. Vascular endothelial growth factor (VEGF) is the most significant angiogenic factor and a selective mitogen for endothelial cells. VEGF, also known as the vascular permeability factor, acts on endothelial cells to increase microvascular permeability and directly stimulate the growth of new blood vessels. Several studies have reported that the expression of VEGF is correlated with hematogenous recurrence via angiogenesis in gastric carcinomas. This research evaluated the relationship between the expression of VEGF and hepatic and peritoneal recurrence in gastric carcinomas. Materials and Methods: Thirty specimens resected from patients with primary gastric carcinomas who had undergone curative resections were divided into three group: Group I, early gastric carcinomas without recurrence; Group II, advanced gastric carcinomas with hepatic recurrence; and Group III, advanced gastric carcinomas with peritoneal recurrence. The expression of VEGF and the density of the microvessel count were examined using immunohistochemistry. Results: 1) The expression of VEGF in Group II and Group III ($63.2\pm\24.3\%$) was stronger than that in Group I ($7\pm\4.2\%$). The expression of VEGF in Group II ($76.5\pm\13.2\%$) was stronger than that of the Group III ($50\pm\14.2\%$) (P<0.05). 2) The microvessel count in Group II ($49.9\pm14.5$) was more than that in Group I ($8.6\pm2.6$) and Group III ($29.1\pm18.1$) (P<0.05). 3) The microvessel count was increased significantly with increasing the expression of VEGF. Conclusions: The expression of VEGF is associated with advanced stomach cancer and hepatic recurrence has a higher expression of VEGF than peritoneal recurrence with neovascularization. Thus the expression of VEGF can be considered to be a useful indicator of recurrence in gastric carcinoma and especially in hepatic recurrence.

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Natural Compounds from Danshen Suppress the Activity of Hepatic Stellate Cells

  • Oh, Seong-Hwan;Cho, Kyung-Hwan;Yang, Beom-Seok;Roh, Yong-Kyun
    • Archives of Pharmacal Research
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    • 제29권9호
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    • pp.762-767
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    • 2006
  • Danshen is an herbal medication frequently used in oriental medicine to treat liver or kidney malfunction. In the course of our studies, we observed that compounds purified from Danshen exhibit an inhibitory activity against Discoidin Domain Receptor 2 (DDR2) tyrosine kinase. Through this inhibition, these compounds also inhibited the growth of HSC T6 cells and suppressed the expression of alpha-smooth muscle actin and MMP2, as well as collagen synthesis, all of which are increased in activated liver stellate cells. Given that activation of liver stellate cells is the hallmark of liver fibrosis and that DDR2 plays a critical role in this activation, these results suggest that one of the pharmacological activities of Danshen extract that protects the liver is the inhibition of key cell-signaling kinases, such as DDR2, in liver stellate cells.

Regulatory roles of NKT cells in Anaplasma phagocytophilum infection

  • Choi, Kyoung-Seong;Chae, Joon-Seok
    • 대한수의학회지
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    • 제49권2호
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    • pp.167-172
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    • 2009
  • Human granulocytic anaplasmosis (HGA) is caused by the obligate intracellular bacterium Anaplasma (A.) phagocytophilum. Natural killer T (NKT) cells are key players in host defense against various microbial infections. We investigated the role of NKT cells in immune response to A. phagocytophilum infection using NKT-knockout ($J\alpha$18-/-) mice. $J\alpha$18-/- and wild-type (WT) mice were infected with low-passage A. phagocytophilum and assayed for hepatic histopathology and cytokine production during 7 days post-infection. Compared to WT controls, the infected $J\alpha$18 -/- mice had much less histopathologic lesions and less apoptosis through day 7, and lower concentrations of ${IFN\gamma}$ and IL- 12, but not of IL-10. This result suggests that NKT cells are major components in the pathogenesis of HGA.

간세포암종의 세침흡인 세포학적 소견 - 247예에 대한 연구 - (Fine Needle Aspiration Cytology of Hepatocellular Carcinoma - A Study on 247 Cases -)

  • 이광길;이종태;최수임;박찬일
    • 대한세포병리학회지
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    • 제1권1호
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    • pp.1-17
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    • 1990
  • Hepatocellular carcinoma (HCC) is malignant tumor frequently occurring in Koreans. There have been few reports regarding the cytologic findings of fine needle aspiration (FNA) of HCC. Most have suggested a diagnostic problem in the cytology distinguishing HCC from some benign hepatic lesions-for example, a regeneration nodule in cirrhosis and liver cell adenoma. In spite of its high frequency in Korea, no cytologic study has been reported, concerning the FNA of HCC. In an attempt to achieve cytologic criteria for the diagnosis of HCC, the authors studied retrospectively cytopathologic findings of 247 cases of HCC. These cases were confirmed either by histoiogic examination including lobectomy, biopsy, or ceil block material, or, when tissue diagnosis was unavailable, by a high serum alpha-fetoprotein level (over 400 I. U.). All aspiration smears were stained by the Papanicolaou method. In each case, the smears were analyzed for cell patterns and various cytomorphology of the tumor cells. The smear background was assessed for the presence of tumor cell necrosis and inflammatory components and compared to that of metastatic carcinomas. The cell patterns were classified as trabecular, acinar, dispersed, and irregular. The cytologic parameters analyzed included the degree of nuclear atypia and the presence of mitoses, intranuclear cytoplasmic inclusions, nucleolar prominency, endothelial lining, multinucleated giant cells, eosinophiic globules, bile, and Mallory body. Most of the FNA of HCC showed markedly cellular smears. The tumor cells were most frequently arranged in a trabecular pattern (80.3%). The irregular (12.6%), the acinar (5.5%), and the dispersed patterns (1.7%) followed in decreasing frequency. Individual hepatoma cells were larger than normal liver cells. However, they had morphologic features characteristic of the hepatic cells the cells were round or polygonal, their cytoplasm was abundant and granular with eosinophilic or amphophilic stainability, and their nuclei were round to oval, located centrally, and tended to have prominent nucleoli. Anaplasia and pleomorphism of tumor cells were generally mild to moderate. These findings existed even in very well differentiated cases. Mitotic figures were present in about 85% of the cases. Prominent nucleoli were observed only in about half the cases. The frequency of other cytologic features was as follows intranuclear cytoplasmic inclusion in 86.8% : endothelial lining in 56.1% : bile in 19.8% : and giant cells in 60.1%. Clear cells were often present in 11.7%, Most aspiration smears of HCC displayed clean background without necrosis or inflammatory material in contrast to the dirty, necrotic background of metastatic cancers and cholangiocarcinomas. Based on the above mentioned features, it is suqqested that the cytologic critieria most important for the diagnosis of HCC include a markedly cellular smear, trabecular pattern, hepatocytoid appearance of tumor cells, endothelial lining, the presence of bile, giant cells, intranuclear cytoplasmic inclusions, and prominent nucleoli, Among these, trabecular pattern, endothelial lining, giant cells and clean smear background are points to be considered in differentiating HCC from metastatic and cholangiocellular carcinoma.

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고려인삼이 ACTH를 받은 마우스의 간 조직 DNA 합성능에 미치는 영향(II) (Influence of Panax Ginseng on Hepatic DNA Synthesis in Mice Receiving ACTH ( II ))

  • 장원상;홍용하;김기연
    • The Korean Journal of Physiology
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    • 제8권2호
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    • pp.75-78
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    • 1974
  • 인삼주정추출액이 ACTH를 받은 마우스의 간 조직 DNA 합성능에 미치는 영향을 알기 위하여 30마리의 마우스 $(18{\sim}20\;gm)$ 수컷을 인삼-ACTH 군과 식염수-ACTH 군으로 나누어 다음과 같은 실험을 하였다. 인삼주정추출액 혹은 식염수 투여가 시작된지 5일째 되는 날에 해당 약물을 주사한 후 1시간만에 ACTH를 투여하고 다시 1시간만에 $[^3H]$ thymidine을 단 1회에 복강속에 주사하고 이어서 이를 마우스를 1, 10, 및 24시간 후에 각각 도살하여 간 조직을 적출하고 자기방사법을 이용하여 방사능 지수를 계수한 바 다음과 같은 결과를 얻었다 1. $[^3H]$ thymidine 주사 후 1, 10 및 24시간만에 관찰된 식염수-ACTH군의 간 조직 방사능 지수는 각각 $1.50{\pm}0.32,\;2.16{\pm}0.33$$2.79{\pm}0.31$이었다. 2. 인삼-ACTH군의 간 조직 방사능 지수는 1, 10 및 24시간만의 값이 각각 $2.71{\pm}0.22,\;3.85{\pm}0.29$$5.06{\pm}0.31$로 나타났다. 그러므로 인삼-ACTH군 간조직 방사능 지수는 식염수-ACTH군의 해당 값보다 현저하게 증가하였다. 이상의 결과로 미루어 보아 인삼-ACTH주사로 인하여 야기되는 마우스의 간 조직 DNA 합성능의 저하를 어느 정도 막는 것으로 추측된다.

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