• 대한약침학회지
• /
• 제21권4호
• /
• pp.284-293
• /
• 2018

Objectives: Thymoquinone (TQ) is one of the active ingredients of herbal plants such as Nigella sativa L. (NS) which has beneficial effects on the body. The beneficial effects of TQ on the cardiovascular system have reported. This study aimed to investigate the effect of TQ on cardiac fibrosis and permeability, serum and tissue concentration of inflammatory markers and oxidative stress status in chronic lipopolysaccharide exposure in male rats. Methods: Seventy male Wistar rats were randomly divided into five groups as follows: (1) control; (2) LPS (1 mg/kg/day); (3-5) LPS + TQ with three doses of 2, 5 and 10 mg/kg (n=14 in each group). After 3 weeks, serum and cardiac levels of $IL-1{\beta}$, $TNF-{\alpha}$ and nitric oxide (NO) metabolites, and cardiac levels of malondialdehyde (MDA), total thiol groups, catalase (CAT) and superoxide dismutase (SOD) activities, permeability of heart tissue (evaluated by Evans blue dye method) and myocardial fibrosis were determined, histologically. Results: LPS administration induced myocardial and perivascular fibrosis and increased cardiac oxidative stress (MDA), inflammatory markers and heart permeability, while, reduced anti-oxidative enzymes (SOD and CAT) and the total thiol group. Administration of TQ significantly attenuated these observations. Conclusion: TQ improved myocardial and perivascular fibrosis through suppression of chronic inflammation and improving oxidative stress status and can be considered for attenuation of cardiac fibrosis in conditions with chronic low-grade inflammation.

• 대한한방내과학회지
• /
• 제43권4호
• /
• pp.643-655
• /
• 2022

Objective: To investigate the protective effects of Haeganjeon on a thioacetamide (TAA)-induced liver fibrosis mouse model and to determine the Haegan-jeon signaling pathway. Methods: Mice were randomly divided into 4 groups: Normal group (Nor), TAA-induced liver fibrosis group (Con), TAA-induced liver fibrosis group administered 50 mg/kg silymarin (S50), TAA-induced liver fibrosis group administered 200 mg/kg Haegan-jeon (H200). The liver fibrosis mouse model was established by intraperitoneal injection with TAA three times a week for 8 weeks. During the 8 weeks, mice were orally administered silymarin and Haegan-jeon every day. At the end of the study, serum was collected to measure the levels of AST, ALT, ammonia, and myeloperoxidase (MPO). Liver tissue was harvested and analyzed by western blotting and Masson's trichrome staining. Results: Administration of Haegan-jeon suppressed the increase in serum levels of AST, ALT, ammonia, and MPO due to TAA-induced liver fibrosis. Compared to the Con group, the H200 group showed increases in antioxidant-related factors (Nrf2, HO-1, catalase, and GPx-1/2) and decreases in inflammatory-related factors (NF-κB p65, p-IκB-α, Cox-2, iNOS, TNF-α, and IL-1β) in western blots. The H200 treatment inhibited the expression of α-SMA and Collagen I. Conclusions: Haegan-jeon showed a hepatoprotective effect induced by activation of antioxidant-related factors, such as Nrf2, and it regulated the inflammation response by suppression of NF-κB.

• BMB Reports
• /
• 제56권2호
• /
• pp.114-119
• /
• 2023

Liver fibrosis is caused by chronic liver damage and results in the aberrant accumulation of extracellular matrix during disease progression. Despite the identification of the HAT enzyme p300 as a major factor for liver fibrosis, the development of therapeutic agents targeting the regulation of p300 has not been reported. We validated a novel p300 inhibitor (A6) on the improvement of liver fibrosis using two mouse models, mice on a choline-deficient high-fat diet and thioacetamide-treated mice. We demonstrated that pathological hall-marks of liver fibrosis were significantly diminished by A6 treatment through Masson's trichrome and Sirius red staining on liver tissue and found that A6 treatment reduced the expression of matricellular protein genes. We further showed that A6 treatment improved liver fibrosis by reducing the stability of p300 protein via disruption of p300 binding to AKT. Our findings suggest that targeting p300 through the specific inhibitor A6 has potential as a major therapeutic avenue for treating liver fibrosis.

• BMB Reports
• /
• 제57권4호
• /
• pp.200-205
• /
• 2024

We conducted a comprehensive series of molecular biological studies aimed at unraveling the intricate mechanisms underlying the anti-fibrotic effects of triamcinolone acetonide (TA) when used in conjunction with fully covered self-expandable metal stents (FCSEMS) for the management of benign biliary strictures (BBS). To decipher the molecular mechanisms responsible for the anti-fibrotic effects of corticosteroids on gallbladder mucosa, we conducted a comprehensive analysis. This analysis included various methodologies such as immunohisto-chemistry, ELISA, real-time PCR, and transcriptome analysis, enabling us to examine alterations in factors related to fibrosis and inflammation at both the protein and RNA levels. Overall, our findings revealed a dose-dependent decrease in fibrosis-related signaling with higher TA concentrations. The 15 mg of steroid treatment (1X) exhibited anti-fibrosis and anti-inflammatory effects after 4 weeks, whereas the 30 mg of steroid treatment (2X) rapidly reduced fibrosis and inflammation within 2 weeks in BBS. Transcriptomic analysis results consistently demonstrated significant downregulation of fibrosis- and inflammation-related pathways and genes in steroid-treated fibroblasts. Use of corticosteroids, specifically TA, together with FCSEMS was effective for the treatment of BBS, ameliorating fibrosis and inflammation. Our molecular biological analysis supports the potential development of steroid-eluted FCSEMS as a therapeutic option for BBS in humans resulting from various surgical procedures.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• 제27권4호
• /
• pp.215-223
• /
• 2024

Purpose: Patients who receive frequent blood transfusions are at an elevated risk of developing hepatic fibrosis due to iron overload in the liver. In this study, we evaluated the effectiveness of transient elastography (TE) (FibroScan^®) for assessing liver fibrosis in patients with pediatric cancer. Methods: We enrolled 106 consecutive cases of acute leukemia in individuals under 21 years of age. The participants were followed for 2 years. Based on their serum ferritin (SF) levels, the patients were divided into two groups: group 1 (SF≥300 ng/mL) and group 2 (SF<300 ng/mL). A liver FibroScan^® was performed, and a p-value of less than 0.05 was considered statistically significant. Results: Among the various parameters in the liver function test (LFT), alkaline phosphatase was significantly higher in a subgroup of patients aged 5-8 years in group 2 compared to those in group 1. The indices of liver fibrosis determined by TE, including the FibroScan score, controlled attenuation parameter score, steatosis percentage, and meta-analysis of histological data in viral hepatitis score, as well as indirect serum markers of liver fibrosis such as the aminotransferase (AST)/alanine aminotransferase (ALT) ratio, Fibrosis 4 score, and AST to platelet ratio index, did not differ significantly between the two groups. The association between the TE results and LFT parameters was only significant for ALT. Conclusion: Transfusion-associated iron overload does not have a significant correlation with severe liver fibrosis. FibroScan^® is not a sensitive tool for detecting early stages of fibrosis in survivors of pediatric leukemia.

• Tuberculosis and Respiratory Diseases
• /
• 제67권4호
• /
• pp.275-280
• /
• 2009

Interstitial lung disease (ILD) is a group of diseases characterized by pulmonary interstitial inflammation. Finally the inflammation results in pulmonary fibrosis and impairment of oxygen transportation. The causes of idiopathic interstitial pneumonia (IIP) are unknown. Diagnosis of IIP is not easy, especially distinguising between nonspecific interstitial pneumonia and usual interstitial pneumonia (UIP). First line treatments of IIP include corticosteroids and immune modulators, which have limited effect. Currently, several drugs are being researched to prevent and treat fibrosis. Newer drugs that may useful to treat pulmonary fibrosis include endothelin receptor antagonist, recombinant soluble TNF receptor antagonist, and cotrimoxazole. The causes of IIP are largely unknown, treatment is not specific, and prognosis is poor. Recent studies are underway to investigate the pathogenesis and treatment of IIP and pulmonary fibrosis. As the pathogenesis of IIP is elucidated, better treatments will emerge.

• Biomolecules & Therapeutics
• /
• 제16권3호
• /
• pp.243-248
• /
• 2008

In the present study, we investigated activity change of sphingomyelin anabolic enzymes such as sphingomyelin synthase and ceramide synthase. Sprague-Dawley male rats treated with 10 mg/kg of DMN intraperitoneally were used as a hepatic fibrosis model. Sphingomyelin synthase and ceramide synthase activities were measured in 1-week, 2-week, 3-week and 4-week DMN-treated rats along with respective control group rats. We found the increased sphingomyelin synthase activity in 4-week DMN-treated liver but not in kidney. Ceramide synthase activity was significantly increased in DMN-treated kidney after 2-week treatment and in DMN-treated liver after 3-week treatment. Although further investigation is necessary to elucidate meanings of sphingolipid metabolites during the liver fibrosis, activity change of sphingolipid anabolic enzymes may imply that sphingolipid metabolism and sphingolipid metabolites could be involved in liver fibrosis especially under oxidative stress.

• Journal of Chest Surgery
• /
• 제34권11호
• /
• pp.883-886
• /
• 2001

종격동 섬유화는 대부분 특발성으로 여러 종격동 구조물, 측 상대정맥, 폐동정맥 등에 병발하여 섬유조직의 포착과 미란, 협착 등으로 증상이 나타난다. 그 중 상대정맥에 가장 흔하게 병 발하지만, 식도에 병발한 특발성 섬유화는 아주 드물게 보고되고 있다. 이러한 특발성 종격동 섬유화로 인한 식도협착은 알 수 없는 염증성 섬유의 증식이지만 그것에 대한 치료방법은 아직 뚜렷이 정해진 바는 없다. 본 보고는 이러한 환자를 부분적 식도해리 및 근절개술로 성공적으로 치료하였다.

• Radiation Oncology Journal
• /
• 제32권3호
• /
• pp.208-212
• /
• 2014

Marfan syndrome is one of the collagen vascular diseases that theoretically predisposes patients to excessive radiation-induced fibrosis yet there is minimal published literature regarding this clinical scenario. We present a patient with a history of Marfan syndrome requiring radiation for a diagnosis of a right brachial plexus malignant nerve sheath tumor. It has been suggested that plasma transforming growth factor beta 1 (TGF-${\beta}1$) can be monitored as a predictor of subsequent fibrosis in this population of high risk patients. We therefore monitored the patient's TGF-${\beta}1$ level during and after treatment. Despite maintaining stable levels of plasma TGF-${\beta}1$, our patient still developed extensive fibrosis resulting in impaired range of motion. Our case reports presents a review of the literature of patients with Marfan syndrome requiring radiation therapy and the limitations of serum markers on predicting long-term toxicity.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권4호
• /
• pp.1589-1593
• /
• 2012

Objective: To investigate liver fibrosis, TGF-${\beta}1$ levels and curative effects on hepatocellular carcinoma (HCC) with small and conventional dose perfusion chemotherapy by transcatheter arterial chemo embolization (TACE). Methods: Thirty-six hepatocellular carcinoma patients not indicated for surgical resection underwent super-selective transcatheter arterial chemoembolization, divided into small dose (n=15) and conventional dose (n=21) chemotherapy groups. Results: With conventional doses, four indices of liver fibrosis focusing on hyaluronate acide (HA), human procollagen type-III (hPC-III), collagen type-Ⅳ (Ⅳ-C) and transforming growth factor-${\beta}l$ (TGF-${\beta}1$) were obviously increased postoperative compared with preoperative (P<0.01); in contrast, with small doses there were no significant differences except for TGF-${\beta}1$. Five year survival demonstrated no significant differences between the two groups (P>0.05). Conclusion: To hepatocellular carcinoma patients treated by TACE, reducing doses of chemotherapy drugs can reduce progress of liver fibrosis, without impacting on five year survival.