• 제목/요약/키워드: fibrosis

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Activity Change of Sphingomyelin Catabolic Enzymes during Dimethylnitrosamine-induced Hepatic Fibrosis in Rats

  • Sacket, Santosh J.;Im, Dong-Soon
    • Biomolecules & Therapeutics
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    • 제16권1호
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    • pp.34-39
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    • 2008
  • Oxidative stress may represent a common link between chronic liver damage and hepatic fibrosis. In the present study, we investigated activity changes of sphingomyelin catabolic enzymes, such as sphingomyelinases and ceramidases by using dimethylnitrosamine (DMN)-treated Sprague-Dawley (SD) male rats hepatic fibrosis model as a hepatic fibrosis model. Twenty rats divided into five groups received: (1) saline; (2) DMN for 1 week, (3) DMN for 2 weeks, (4) DMN for 3 weeks, and (5) DMN for 4 weeks by intraperitoneally 10 mg/kg of body weight for three consecutive days a week. Activities of acidic and neutral sphingomyelinases and acidic, neutral and alkaline ceramidases were measured in the liver and kidney from DMN-treated rats. We found increased ceramidase activities from 2-week and/or 3-week DMN treated rat livers compared to control rat liver. Acidic sphingomyelinase and alkaline ceramidase activities were significantly increased in 3-week DMN-treated rat kidneys compared to control rat kidney. Therefore, sphingolipid metabolizing enzymes and sphingolipid metabolites are supposed to be involved in liver fibrosis, although further investigation is necessary to elucidate meanings of sphingolipids during the liver fibrosis

Burkholderia cepacia Complex Infection in a Cohort of Italian Patients with Cystic Fibrosis

  • Lambiase, Antonietta;Raia, Valeria;Stefani, Stefania;Sepe, Angela;Ferri, Pasqualina;Buonpensiero, Paolo;Rossano, Fabio;Pezzo, Mariassunta Del
    • Journal of Microbiology
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    • 제45권3호
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    • pp.275-279
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    • 2007
  • The aims of this study were to detect Burkholderia cepacia complex (Bcc) strains in a cohort of Cystic Fibrosis patients (n=276) and to characterize Bcc isolates by molecular techniques. The results showed that 11.23% of patients were infected by Bcc. Burkholderia cenocepacia lineage III-A was the most prevalent species (64.3%) and, of these, 10% was cblA positive and 50% esmR positive. Less than half of the strains were sensitive to ceftazidime, meropenem, piperacillin-tazobactam, and trimethoprim-sulfamethoxazole. About half of the strains (41%) had homogeneous profiles, suggesting cross-transmission. The infection by B. cenocepacia was associated to a high rate of mortality (p=0.01).

Long non-coding RNAs: key regulators of liver and kidney fibrogenesis

  • Su-hyang Han;Je Yeong Ko;Eun Seo Kang;Jong Hoon Park;Kyung Hyun Yoo
    • BMB Reports
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    • 제56권7호
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    • pp.374-384
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    • 2023
  • Fibrosis is a pathological condition that is characterized by an abnormal buildup of extracellular matrix (ECM) components, such as collagen, in tissues. This condition affects various organs of the body, including the liver and kidney. Early diagnosis and treatment of fibrosis are crucial, as it is a progressive and irreversible process in both organs. While there are certain similarities in the fibrosis process between the liver and kidney, there are also significant differences that must be identified to determine molecular diagnostic markers and potential therapeutic targets. Long non-coding RNAs (lncRNAs), a class of RNA molecules that do not code for proteins, are increasingly recognized as playing significant roles in gene expression regulation. Emerging evidence suggests that specific lncRNAs are involved in fibrosis development and progression by modulating signaling pathways, such as the TGF-β/Smad pathway and the β-catenin pathway. Thus, identifying the precise lncRNAs involved in fibrosis could lead to novel therapeutic approaches for fibrotic diseases. In this review, we summarize lncRNAs related to fibrosis in the liver and kidney, and propose their potential as therapeutic targets based on their functions.

Protective effect of Tranilast on radiation-induced heart fibrosis in C57BL/6 mouse

  • Moon, Seongkwon
    • International Journal of Contents
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    • 제8권4호
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    • pp.64-69
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    • 2012
  • The heart is a major dose-limiting organ for radiotherapy of cancer in the thoracic region. The purpose of this study was to examine the protective effect of tranilast on the radiation-induced heart fibrosis model using the C57BL/6 murine strain. A significant reduction in the expression of TGF-${\beta}1$, collagen type I and collagen type III was observed in the radiation plus tranilast group. The authors also suggest the use of tranilast in a clinical trial for the prevention of radiation-induced heart fibrosis.

Two-Dimensional Shear Wave Elastography Predicts Liver Fibrosis in Jaundiced Infants with Suspected Biliary Atresia: A Prospective Study

  • Huadong Chen;Luyao Zhou;Bing Liao;Qinghua Cao;Hong Jiang;Wenying Zhou;Guotao Wang;Xiaoyan Xie
    • Korean Journal of Radiology
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    • 제22권6호
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    • pp.959-969
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    • 2021
  • Objective: This study aimed to evaluate the role of preoperative two-dimensional (2D) shear wave elastography (SWE) in assessing the stages of liver fibrosis in patients with suspected biliary atresia (BA) and compared its diagnostic performance with those of serum fibrosis biomarkers. Materials and Methods: This study was approved by the ethical committee, and written informed parental consent was obtained. Two hundred and sixteen patients were prospectively enrolled between January 2012 and October 2018. The 2D SWE measurements of 69 patients have been previously reported. 2D SWE measurements, serum fibrosis biomarkers, including fibrotic markers and biochemical test results, and liver histology parameters were obtained. 2D SWE values, serum biomarkers including, aspartate aminotransferase to platelet ratio index (APRi), and other serum fibrotic markers were correlated with the stages of liver fibrosis by METAVIR. Receiver operating characteristic (ROC) curves and area under the ROC (AUROC) curve analyses were used. Results: The correlation coefficient of 2D SWE value in correlation with the stages of liver fibrosis was 0.789 (p < 0.001). The cut-off values of 2D SWE were calculated as 9.1 kPa for F1, 11.6 kPa for F2, 13.0 kPa for F3, and 15.7 kPa for F4. The AUROCs of 2D SWE in the determination of the stages of liver fibrosis ranged from 0.869 to 0.941. The sensitivity and negative predictive value of 2D SWE in the diagnosis of ≥ F3 was 93.4% and 96.0%, respectively. The diagnostic performance of 2D SWE was superior to that of APRi and other serum fibrotic markers in predicting severe fibrosis and cirrhosis (all p < 0.005) and other serum biomarkers. Multivariate analysis showed that the 2D SWE value was the only statistically significant parameter for predicting liver fibrosis. Conclusion: 2D SWE is a more effective non-invasive tool for predicting the stage of liver fibrosis in patients with suspected BA, compared with serum fibrosis biomarkers.

Biological Safety and Anti-hepatofibrogenic Effects of Brassica rapa (Turnip) Nanoparticle

  • Park, Dae-Hun;Li, Lan;Jang, Hyung-Kwan;Kim, Young-Jin;Jang, Ja-June;Choi, Yeon-Shik;Park, Seung-Kee;Lee, Min-Jae
    • Molecular & Cellular Toxicology
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    • 제5권4호
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    • pp.317-322
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    • 2009
  • Hepatic fibrosis is one of chronic liver diseases which spread in worldwide and it has high risk to turn advanced cirrhosis and hepatocellualr carcinoma. Brassica family has been produced for commercial purpose and in Korea Brassica rapa (Turnip) is cultivated in Ganghwa County, Gyeonggi-do Korea and used for making Kimchi. Recently pharmacological effects of turnip have been known; diabete mellitus modulation, alcohol oxidization, and fibrosis inhibition. In previous study we found antifibrogenic effect of turnip water extract and in this study we made turnip nanoparticle to promote turnip delivery into liver. At the same time we assessed the biological safety of turnip nanoparticle. Thioacetamide (TAA) induced hepatic nodular formation and fibrosis (mean of fibrosis score: 4). However, 1% turnip nanoparticle inhibited TAA-induced hepatic nodular formation and fibrosis (mean of fibrosis score: 2-3). Activities of serum enzymes (aspartic acid transaminase (AST), alanine transaminase (ALT), and total bilirubin (T-Bil)), complete blood count (CBC), and the appearance of organs were not different from control and 1% turnip nanoparticle treatment. Conclusively 1% turnip nanoparticle significantly reduced TAA-induced hepatic fibrosis and was safe in 7-weeks feeding.

맥문동(麥門冬)이 C57BL/6J 생쥐의 Bleomycin 폐섬유화(肺纖維化)에 미치는 영향(影響) (The Inhibitory Effects of Liriopis Tuber on the Bleomycin-induced lung fibrosis in C57BL/6J mice)

  • 이형구;정승기;정희재;이병삼
    • 대한한방내과학회지
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    • 제25권4호
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    • pp.93-104
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    • 2004
  • Objectives : The aim was to identify the inhibitory effects of Liriopis Tuber on bleomycin-induced lung fibrosis by analysing the changes of imflammatory cell cytokines and SHI(Semiquantitative Histological Index), Materials and Methods : In this study fibrosis prone C57BL/6J mice were used. Control group was treated with blomycin(0.06mg/0.1 ml) by IT(intratracheal) instillation which is a popular method of inducing lung fibrosis and sample group took Liriopis Tuber water extract(38.0mg/10g body weight) orally for 14 days after IT instillation of blomycin. We measured the total and differential count of WBC, $IFN-{\gamma}$ & IL-4 in mice BALF and SHI(Semiquantitative Histological Index) from lung tissues of mice. BALF and lung tissues of mice were taken 14 days after IT instillation of blomycin. Results : In sample group total WBC count, proportion of neutrophil, SHI and IL-4 significantly(p<0.05) decreased, proportion of macrophage significantly(p<0.05) increased and proportion of lymphocyte, $IFN-{\gamma}$ did not decrease significantly. Conclusions : This study suggests that Liriopis Tuber has an inhibitory effects of pulmonary fibrosis by attenuation of inflammation and Th2 immune response. To determine whether this herbal medicine contribute to cure and prophylaxis of pulmonary fibrosis, further studies on the role of $IFN-{\gamma}$ relating to fibrosis are required.

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Cyclooxygenase-2 over-expression is associated with increased mast cells in CCl4-induced hepatic fibrosis

  • Jekal, Seung-Joo;Lee, Jae-Hyoung;Park, Seung-Teack
    • 대한임상검사과학회지
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    • 제44권4호
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    • pp.229-238
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    • 2012
  • Cyclooxygenase(COX-2) is an inducible enzyme that catalyzes the synthesis of prostaglandins (PGs) from arachidonic acid. Over-expression of COX-2 has been reported to be associated with progressive hepatic fibrosis in chronic hepatic C infection and rat liver fibrosis induced by carbon tetrachloride($CCl_4$). Recently, it is well known that mast cell products can stimulate the proliferation of hepatic stellate cells and key players in liver fibrosis. But little is known regarding their role in $CCl_4$-induced liver fibrosis in rat. Our aim was to investigate the relation between COX-2 expression and mast cells during liver fibrosis after $CCl_4$ treatment. Thirty Wistar rats were divided into five groups (non-treated 0, 2, 4, 6 and 8-week after $CCl_4$-treatment). Reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry were used to assess the expression of ${\alpha}$-smooth muscle actin (${\alpha}$-SMA), collagen-1 and COX-2 in liver tissue from $CCl_4$-treated rats. The density of collagen and mast cells were determined using a computerized image analysis system in liver sections stained with picrosirius red and toluidine blue, respectively. The expression levels of ${\alpha}$-SMA, collagen-1 and COX-2 mRNA were significantly higher at 2 wk in $CCl_4$-treated groups than non-treated group. The number of mast cells in liver tissues increased gradually from 2 wk to 6 wk depending on the fibrosis severity but decreased abruptly at 8 wk. The significant increase of collagen-1 and ${\alpha}$-SMA mRNA expression in $CCl_4$-treated rats was continued until 6 wk while the COX-2 mRNA was significantly decreased at 8 wk. These results suggest that increased mast cells are closely associated with COX-2 over-expression during hepatic fibrogenesis of $CCl_4$-treated rats.

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Amelioration of Bleomycin-induced Pulmonary Fibrosis of Rats by an Aldose Reductase Inhibitor, Epalrestat

  • Li, Xianwei;Shen, Yuanyuan;Lu, Yining;Yang, Jieren
    • The Korean Journal of Physiology and Pharmacology
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    • 제19권5호
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    • pp.401-411
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    • 2015
  • Aldose reductase (AR) is known to play a crucial role in the mediation of diabetic and cardiovascular complications. Recently, several studies have demonstrated that allergen-induced airway remodeling and ovalbumin-induced asthma is mediated by AR. Epalrestat is an aldose reductase inhibitor that is currently available for the treatment of diabetic neuropathy. Whether AR is involved in pathogenesis of pulmonary fibrosis and whether epalrestat attenuates pulmonary fibrosis remains unknown. Pulmonary fibrosis was induced by intratracheal instillation of bleomycin (5 mg/kg) in rats. Primary pulmonary fibroblasts were cultured to investigate the proliferation by BrdU incorporation method and flow cytometry. The expression of AR, TGF-${\beta}_1$, ${\alpha}$-SMA and collagen I was analyzed by immunohistochemisty, real-time PCR or western blot. In vivo, epalrestat treatment significantly ameliorated the bleomycin-mediated histological fibrosis alterations and blocked collagen deposition concomitantly with reversing bleomycin-induced expression up-regulation of TGF-${\beta}_1$, AR, ${\alpha}$-SMA and collagen I (both mRNA and protein). In vitro, epalrestat remarkably attenuated proliferation of pulmonary fibroblasts and expression of ${\alpha}$-SMA and collagen I induced by TGF-${\beta}_1$, and this inhibitory effect of epalrestat was accompanied by inhibiting AR expression. Knockdown of AR gene expression reversed TGF-${\beta}_1$-induced proliferation of fibroblasts, up-regulation of ${\alpha}$-SMA and collagen I expression. These findings suggest that AR plays an important role in bleomycin-induced pulmonary fibrosis, and epalrestat inhibited the progression of bleomycin-induced pulmonary fibrosis is mediated via inhibiting of AR expression.