• Title/Summary/Keyword: fibrosis

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Not All Children with Cystic Fibrosis Have Abnormal Esophageal Neutralization during Chemical Clearance of Acid Reflux

  • Woodley, Frederick W.;Moore-Clingenpeel, Melissa;Machado, Rodrigo Strehl;Nemastil, Christopher J.;Jadcherla, Sudarshan R.;Hayes, Don Jr;Kopp, Benjamin T.;Kaul, Ajay;Di Lorenzo, Carlo;Mousa, Hayat
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.20 no.3
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    • pp.153-159
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    • 2017
  • Purpose: Acid neutralization during chemical clearance is significantly prolonged in children with cystic fibrosis, compared to symptomatic children without cystic fibrosis. The absence of available reference values impeded identification of abnormal findings within individual patients with and without cystic fibrosis. The present study aimed to test the hypothesis that significantly more children with cystic fibrosis have acid neutralization durations during chemical clearance that fall outside the physiological range. Methods: Published reference value for acid neutralization duration during chemical clearance (determined using combined impedance/pH monitoring) was used to assess esophageal acid neutralization efficiency during chemical clearance in 16 children with cystic fibrosis (3 to < 18 years) and 16 age-matched children without cystic fibrosis. Results: Duration of acid neutralization during chemical clearance exceeded the upper end of the physiological range in 9 of 16 (56.3%) children with and in 3 of 16 (18.8%) children without cystic fibrosis (p=0.0412). The likelihood ratio for duration indicated that children with cystic fibrosis are 2.1-times more likely to have abnormal acid neutralization during chemical clearance, and children with abnormal acid neutralization during chemical clearance are 1.5-times more likely to have cystic fibrosis. Conclusion: Significantly more (but not all) children with cystic fibrosis have abnormally prolonged esophageal clearance of acid. Children with cystic fibrosis are more likely to have abnormal acid neutralization during chemical clearance. Additional studies involving larger sample sizes are needed to address the importance of genotype, esophageal motility, composition and volume of saliva, and gastric acidity on acid neutralization efficiency in cystic fibrosis children.

Inhibitory Effect of Injinchunggantang-derivative on Hepatic Fibrosis (인진청간탕가미방이 간조직의 섬유화 억제에 미치는 영향)

  • 강경태;김영철;이장훈;우홍정
    • The Journal of Korean Medicine
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    • v.23 no.2
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    • pp.39-56
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    • 2002
  • Objective : The aim of this study is to investigate the inhibitory effect of lnjinchunggantang-derivative on acute and sub-acute hepatic fibrosis induced by $CCl_4$, and to compare the efficiency of lnjinchunggantang-derivative, Salviae Radix and Scirpi Tuber.Zeloariae Rhizoma on acute and sub-acute hepatic fibrosis induced by $CCl_4$. Method : Western blotting for collagen type N, quantitative RT-PCR and gross & histological findings on liver tissue (Hematoxylin & Eosin stain, Reticulin stain, Masson-Trichrome stain) were studied. Results : In the study on collagen type N expression, lnjinchunggantangcderivative, Scirpi Tuber.Zeloariae Rhizoma and Salviae Radix showed inhibitory effect in western blotting. In quantitative RT-PCR assay, lnjinchunggantang-derivative showed inhibitory effect on collagen type N expression in acute hepatic fibrosis model, whereas lnjinchunggantang-derivative, Scirpi Tuber.Zeloariae Rhizoma and Salviae Radix showed inhibitory effect on collagen type N expression in sub-acute hepatic fibrosis model. In the gross findings of acute and sub-acute hepatic fibrosis models,lnjinchunggantang-derivative, Salviae Radix and Scirpi Tuber. Zeloariae Rhizoma showed inhibitory effect on hepatic fibrosis in the order. In the histological findings of acute and sub-acute hepatic fibrosis models in Hematoxylin & Eosin, Reticulin and Masson-Trichrome staining, the liver of $CCl_4$-only group showed atrophy and necrotic change with white nodules whereas that of $CCl_4$+ Injinchunggantang-derivative showed no significant histological change with well preservation of the tone of the tissue, and Scirpi Tuber. Zeloariae Rhizoma and Salviae Radix group showed minimal fibrotic changes. In the scoring system of the extent of the inhibition of the hepatic fibrosis, lnjinchunggantang-derivative group showed statistically significant inhibitory effect(p<0.05) whereas Scirpi Tuber.Zeloariae Rhizoma and Salviae Radix group showed no statistically significant effect in the acute hepatic fibrosis model. In the sub-acute hepatic fibrosis model, lnjinchunggantang-derivative, Scirpi Tuber.Zeloariae Rhizoma and Salviae Radix group showed statistically significant effect (p<0.01). Conclusion : These results show that lnjinchunggantang-derivative, Salviae Radix and Scirpi Tuber.Zeloariae Rhizoma have inhibitory effect in the order on hepatic fibrosis induced by $CCl_4$ by suppressing the expression of collagen type N, ultimately preventing liver cirrhosis. To obtain more credible results in this experiment, developement of a new experimental model more similar to human hepatic fibrosis is still needed.

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Ginsenosides: potential therapeutic source for fibrosis-associated human diseases

  • Li, Xiaobing;Mo, Nan;Li, Zhenzhen
    • Journal of Ginseng Research
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    • v.44 no.3
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    • pp.386-398
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    • 2020
  • Tissue fibrosis is an eventual pathologic change of numerous chronic illnesses, which is characterized by resident fibroblasts differentiation into myofibroblasts during inflammation, coupled with excessive extracellular matrix deposition in tissues, ultimately leading to failure of normal organ function. Now, there are many mechanistic insights into the pathogenesis of tissue fibrosis, which facilitate the discovery of effective antifibrotic drugs. Moreover, many chronic diseases remain a significant clinical unmet need. For the past five years, many research works have undoubtedly addressed the functional dependency of ginsenosides in different types of fibrosis and the successful remission in various animal models treated with ginsenosides. Caveolin-1, interleukin, thrombospondin-1 (TSP-1), liver X receptors (LXRs), Nrf2, microRNA-27b, PPARδ-STAT3, liver kinase B1 (LKB1)-AMPK, and TGF-β1/Smads are potential therapy targeting using ginsenosides. Ginsenosides can play a targeting role and suppress chronic inflammatory response, collagen deposition, and epitheliale-mesenchymal transition (EMT), as well as myofibroblast activation to attenuate fibrosis. In this report, our aim was to focus on the therapeutic prospects of ginsenosides in fibrosis-related human diseases making use of results acquired from various animal models. These findings should provide important therapeutic clues and strategies for the exploration of new drugs for fibrosis treatment.

Bioimpedance Changes in Rats with CCl4-Induced Liver Fibrosis

  • Heo, Jeong;Jung, Dong-Keun
    • Journal of Sensor Science and Technology
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    • v.20 no.2
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    • pp.71-76
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    • 2011
  • To characterize the relationship between the stage of hepatic fibrosis and bioimpedance, several electric parameters were estimated in rats with $CCl_4$-induced liver fibrosis. Thirty three Sprague-Dawley rats were intraperitoneally injected with a $CCl_4$-mineral oil mixture (1:1, 0.2 mL/100 g) twice a week for 8 weeks. The resistance(R), reactance(X), impedance(Z), and dissipation factor(D) between 1 kHz and 100 kHz were then evaluated in the livers of the rats under pentobarbital anesthesia using an HP4294A Impedance Analyzer. The rats were killed 2, 4, 6, and 8 weeks later, and their livers were classified in accordance with Ishak's scoring system. R, X, and Z changed in accordance with the progression of hepatic fibrosis and the changes were greater at lower frequencies than at higher frequencies. In comparison, the D spectrum was biphasic; D increased initially then decreased with increasing frequency. All of the parameters(R, X, Z, and D) changed in accordance with the stage of fibrosis in the livers, but D changed specifically with the progression of fibrosis. These results indicate that hepatic fibrosis may be evaluated by determining the changes in D.

Usefulness of Liver Fibrosis According to Classification of Image Score System In Abdominal Ultrasonography (복부 초음파검사에서 영상 점수 시스템 분류에 따른 간 섬유화 평가의 유용성)

  • An, Hyun;Ji, Tae-jeong;Lee, Hyo-young;Im, In-chul
    • Journal of radiological science and technology
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    • v.42 no.3
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    • pp.187-194
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    • 2019
  • The purpose of this study was to evaluate the pathologic results of hepatic parenchyma parameters such as liver parenchyma, liver surface, liver margin and liver, portal vein, spleen size, And to evaluate the usefulness of fibrosis progression and hepatic ultrasonography. The sensitivity, specificity, positive predictive value, and prognostic value according to the stage of fibrosis and grade of inflammation were divided into two groups according to the morphologic variable "A" through ultrasound and "B" We evaluated the predictive value and predicted the variables to evaluate fibrosis in clinical diagnosis and treatment of patients with chronic liver disease. The sensitivity and specificity of hepatic fibrosis in hepatic morphologic variables and other size variables were highest in liver surface and edge. The morphologic parameters used in the evaluation of fibrosis were clinically relevant in distinguishing the fibrosis stage from the results of liver biopsy.

Analysis on Usefulness of Non-invasive Liver Fibrosis Evaluation Method according to the Liver Disease : Focused on Hepatitis C patients (간질환 종류에 따른 비침습적 간섬유화 평가법의 유용성 분석 : C형 간염 보균자 중심으로)

  • Nam, Ji-Hee;Kim, Jung-Hoon
    • Journal of radiological science and technology
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    • v.42 no.5
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    • pp.345-350
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    • 2019
  • Liver biopsy is the gold standard for diagnosing liver fibrosis, but it is invasive and has a risk for complications. For this reason, recently, study has been actively conducted on non-invasive liver fibrosis evaluation method. But, there is no established standard for the type of diffuse liver disease. Therefore, this study was suggest the usefulness and cut-off values of Fibroscan, FIB-4, APRI and AAR of patients with hepatitis C in Korea. According to the diagnosis, 240 people in hepatitis C are classified into fatty liver, chronic hepatitis, and liver cirrhosis. The statistical analysis was performed by ANOVA to verify difference between groups. The ROC curve was analyzed to determine the usefulness and practical cut-off value. As a result, for all diseases, the AUC value for Fibroscan was 0.8 over and the APRI was 0.7 over. Cut-off value of serum based liver fibrosis markers was increased in order of fatty liver, chronic hepatitis and liver cirrhosis. If Fibroscan and serological liver fibrosis markers are applied to predict liver fibrosis, it is expected that excessive liver biopsy can be reduced.

Medical Imaging and Nuclear Molecular Imaging Probes for Pulmonary Fibrosis Diagnosis

  • Heesu Ahn;Yong Jin Lee
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.8 no.2
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    • pp.103-111
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    • 2022
  • Idiopathic pulmonary fibrosis (IPF) is a progressive disease caused by some risk factors, including smoking, viral infection, toxic substances, and radiation, that decline lung function of fresh oxygen and blood delivery throughout the body. Patients with pulmonary fibrosis have suffered from breathing and cough and the average survival rate is only 3 years after diagnosis. Therefore, it is significant to diagnose IPF and start treatment in enough time. Usually, lung biopsy is available to diagnose localized pulmonary fibrotic sites directly. However, it is insufficient to visualize whole lung tissue, and also it has a risk of infection for patients. In the clinic, medical imaging systems can diagnose pulmonary fibrosis non-invasively without infection. In this review, we introduce current medical imaging systems used to diagnose pulmonary fibrosis, including CT, MRI, and nuclear medicine. Further, we introduce several molecular imaging probes targeting specific biomarkers which are expressed in pulmonary fibrosis. Through this paper, it is expected that it would be helpful to understand the latest knowledge and research trends on pulmonary fibrosis diagnostic imaging.

Genistein alleviates pulmonary fibrosis by inactivating lung fibroblasts

  • Seung-hyun Kwon;Hyunju Chung;Jung-Woo Seo;Hak Su Kim
    • BMB Reports
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    • v.57 no.3
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    • pp.143-148
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    • 2024
  • Pulmonary fibrosis is a serious lung disease that occurs predominantly in men. Genistein is an important natural soybean-derived phytoestrogen that affects various biological functions, such as cell migration and fibrosis. However, the antifibrotic effects of genistein on pulmonary fibrosis are largely unknown. The antifibrotic effects of genistein were evaluated using in vitro and in vivo models of lung fibrosis. Proteomic data were analyzed using nano-LC-ESI-MS/MS. Genistein significantly reduced transforming growth factor (TGF)-β1-induced expression of collagen type I and α-smooth muscle actin (SMA) in MRC-5 cells and primary fibroblasts from patients with idiopathic pulmonary fibrosis (IPF). Genistein also reduced TGF-β1-induced expression of p-Smad2/3 and p-p38 MAPK in fibroblast models. Comprehensive protein analysis confirmed that genistein exerted an anti-fibrotic effect by regulating various molecular mechanisms, such as unfolded protein response, epithelial mesenchymal transition (EMT), mammalian target of rapamycin complex 1 (mTORC1) signaling, cell death, and several metabolic pathways. Genistein was also found to decrease hydroxyproline levels in the lungs of BLM-treated mice. Genistein exerted an anti-fibrotic effect by preventing fibroblast activation, suggesting that genistein could be developed as a pharmacological agent for the prevention and treatment of pulmonary fibrosis.

Eupatilin treatment inhibits transforming growth factor beta-induced endometrial fibrosis in vitro

  • Lee, Chang-Jin;Hong, Seon-Hwa;Yoon, Min-Ji;Lee, Kyung-Ah;Choi, Dong Hee;Kwon, Hwang;Ko, Jung-Jae;Koo, Hwa Seon;Kang, Youn-Jung
    • Clinical and Experimental Reproductive Medicine
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    • v.47 no.2
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    • pp.108-113
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    • 2020
  • Objective: Endometrial fibrosis, the primary pathological feature of intrauterine adhesion, may lead to disruption of endometrial tissue structure, menstrual abnormalities, infertility, and recurrent pregnancy loss. At present, no ideal therapeutic strategy exists for this fibrotic disease. Eupatilin, a major pharmacologically active flavone from Artemisia, has been previously reported to act as a potent inducer of dedifferentiation of fibrotic tissue in the liver and lung. However, the effects of eupatilin on endometrial fibrosis have not yet been investigated. In this study, we present the first report on the impact of eupatilin treatment on transforming growth factor beta (TGF-β)-induced endometrial fibrosis. Methods: The efficacy of eupatilin on TGF-β-induced endometrial fibrosis was assessed by examining changes in morphology and the expression levels of fibrosis markers using immunofluorescence staining and quantitative real-time reverse-transcription polymerase chain reaction. Results: Eupatilin treatment significantly reduced the fibrotic activity of TGF-β-induced endometrial fibrosis in Ishikawa cells, which displayed more circular shapes and formed more colonies. Additionally, the effects of eupatilin on fibrotic markers including alpha-smooth muscle actin, hypoxia-inducible factor 1 alpha, collagen type I alpha 1 chain, and matrix metalloproteinase-2, were evaluated in TGF-β-induced endometrial fibrosis. The expression of these markers was highly upregulated by TGF-β pretreatment and recovered to the levels of control cells in response to eupatilin treatment. Conclusion: Our findings suggest that suppression of TGF-β-induced signaling by eupatilin might be an effective therapeutic strategy for the treatment of endometrial fibrosis.

Genome-Wide Transcriptional Response During the Development of Bleomycin-Induced Pulmonary Fibrosis in Sprague-Dawley Rats

  • Park, Han-Jin;Yang, Mi-Jin;Oh, Jung-Hwa;Yang, Young-Su;Kwon, Myung-Sang;Song, Chang-Woo;Yoon, Seok-Joo
    • Toxicological Research
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    • v.26 no.2
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    • pp.137-147
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    • 2010
  • Pulmonary fibrosis is a common consequence of many lung diseases and a leading cause of morbidity and mortality. The molecular mechanisms underlying the development of pulmonary fibrosis remain poorly understood. One model used successfully to study pulmonary fibrosis over the past few decades is the bleomycin-induced pulmonary fibrosis model. We aimed to identify the genes associated with fibrogenesis using an Affymetrix GeneChip system in a bleomycin-induced rat model for pulmonary fibrosis. To confirm fibrosis development, several analyses were performed, including cellular evaluations using bronchoalveolar lavage fluid, measurement of lactate dehydrogenase activity, and histopathological examinations. Common aspects of pulmonary fibrosis such as prolonged inflammation, immune cell infiltration, emergence of fibroblasts, and deposition of extracellular matrix and connective tissue elements were observed. Global gene expression analysis revealed significantly altered expression of genes ($\geq$ 1.5-fold, p < 0.05.) in a time-dependent manner during the development of pulmonary fibrosis. Our results are consistent with previous results of well-documented gene expression. Interestingly, the expression of triggering receptor expressed on myeloid cells 2 (Trem2), secreted phosphoprotein 1 (Spp1), and several proteases such as Tpsab1, Mcpt1, and Cma1 was considerably induced in the lung after bleomycin treatment, despite little evidence that they are involved in pulmonary fibrogenesis. These data will aid in our understanding of fibrogenic mechanisms and contribute to the identification of candidate biomarkers of fibrotic disease development.