scholarly journals Chymase as a Novel Therapeutic Target in Acute Pancreatitis

2021 ◽  
Vol 22 (22) ◽  
pp. 12313
Author(s):  
Toru Kuramoto ◽  
Denan Jin ◽  
Koji Komeda ◽  
Kohei Taniguchi ◽  
Fumitoshi Hirokawa ◽  
...  

Acute pancreatitis is still a life-threatening disease without an evidenced therapeutic agent. In this study, the effect of chymase in acute pancreatitis and the possible effect of a chymase inhibitor in acute pancreatitis were investigated. Hamsters were subcutaneously administered 3.0 g/kg of L-arginine to induce acute pancreatitis. Biological markers were measured 1, 2, and 8 h after L-arginine administration. To investigate the effect of a chymase inhibitor, a placebo (saline) or a chymase inhibitor TY-51469 (30 mg/kg) was given 1 h after L-arginine administration. The survival rates were evaluated for 24 h after L-arginine administration. Significant increases in serum lipase levels and pancreatic neutrophil numbers were observed at 1 and 2 h after L-arginine administration, respectively. Significant increases in pancreatic neutrophil numbers were observed in the placebo-treated group, but they were significantly reduced in the TY-51469-treated group. A significant increase in the pancreatic tumor necrosis factor-α mRNA level was observed in the placebo-treated group, but it disappeared in the TY-51469-treated group. Chymase activity significantly increased in the placebo-treated group, but it was significantly reduced by treatment with TY-51469. The survival rate significantly improved in the TY-51469-treated group. A chymase inhibitor may become a novel therapeutic agent for acute pancreatitis.

2010 ◽  
Vol 7 (3) ◽  
pp. 341-349 ◽  
Author(s):  
Zhu Shijie ◽  
Junji Moriya ◽  
Jun’ichi Yamakawa ◽  
Rui Chen ◽  
Takashi Takahashi ◽  
...  

Goal of this study was to evaluate effects of Mao-to on development of myocarditis induced by encephalomyocarditis (EMC) virus in mice. Mice were randomly divided into five groups. Group N included uninfected controls (n= 18), while group A, B and C underwent intraperitoneal injection of EMC virus. Group A was administered oral saline from day 0 to day 4. Group B was administered oral Mao-to (500 mg−1kg−1day−1) from day 0 to day 4. Group C was administered Mao-to from day 2 to day 6. Group D was administered Mao-to from day 5 to day 10. Treated mice were followed for survival rates during 2 weeks after infection. Body weight (BW) and organ weights including heart (HW), lungs, thymus and spleen were examined on days 4, 6 and 14. Survival rate of group C (36.4%) was significantly improved compared with group A, B or D (0% of each,P< 0.05). HW and HW/BW ratio in group C was significantly (P< 0.05) lower than those in group A, B or D. Viral titers of hearts were significantly different among groups A, B and C. Cardiac expression in tumor necrosis factor-α (TNF-α) was significantly reduced in group C in comparison with group A, B or D on day 6 by immunohistochemical study. Administration of Mao-to starting on day 2 improves mortality resulting from viral myocarditis in mice with reduced expression of cardiac TNF-α. These findings suggest that timing of Mao-to is crucial for preventing cardiac damage in mice with viral myocarditis.


Life Sciences ◽  
2021 ◽  
pp. 119500
Author(s):  
Fereshteh Asgharzadeh ◽  
Alireza Hashemzadeh ◽  
Farzad Rahmani ◽  
Atieh Yaghoubi ◽  
Seyedeh Elnaz Nazari ◽  
...  

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1208
Author(s):  
Mina Kim ◽  
Ji Yeong Kim ◽  
Hee Sun Yang ◽  
Jeong-Sook Choe ◽  
In Guk Hwang

Salvia plebeia has been used to treat a variety of inflammatory diseases, as well as colds and bronchitis. Macrophages have antioxidant defense mechanisms to cope with the intracellular reactive oxygen species (ROS) produced as part of the immune response. The nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase (HO)-1 pathway in inflamed macrophages is an appealing target due to its protective effect against ROS-induced cell damage. In this study, nepetoidin B (NeB) was first isolated from S. plebeia and identified by nuclear magnetic resonance spectroscopy. NeB reduced pro-inflammatory mediators (nitric oxide and prostaglandin E2) and cytokines (tumor necrosis factor-α, interleukin (IL)-6, and IL-1β) in LPS-activated RAW 264.7 cells by inhibiting the NF-κB signaling pathway. In the NeB-treated group, catalase and superoxide dismutase levels were significantly higher, and ROS expression decreased. By activating Nrf2 signaling, NeB enhanced HO-1 expression. Furthermore, when the cells were pretreated with tin protoporphyrin (an HO-1 inhibitor), the anti-inflammatory effects of NeB were reduced. Therefore, NeB may activate the Nrf2/ HO-1 pathway. These results reveal the NeB isolated from S. plebeia exerts anti-inflammatory effects by modulating NF-κB signaling and activating the Nrf2/HO-1 pathway in LPS-stimulated RAW 264.7 cells.


2021 ◽  
Vol 30 ◽  
pp. 096368972098511
Author(s):  
Gang Li ◽  
Xu Zhang ◽  
Xiangyang Guo ◽  
Yi Li ◽  
Chong Li

Bladder cancer is one of the most common malignancies. The existence of bladder cancer stem cells (BCSCs) has been suggested to underlie bladder tumor initiation and recurrence. Propofol is a commonly used intravenous anesthetic. Here, we find that propofol can dramatically block the activation of Hedgehog pathway in BCSCs. The propofol strongly repressed the growth of cancer cells. Attenuated proliferation and enhanced apoptosis of tumor cells were observed upon propofol stimulation. Furthermore, propofol reduced the self-renewal ability of BCSCs as well as the tumor formation. In conclusion, propofol is potentially used as a novel therapeutic agent for bladder cancer by targeting self-renewal through inhibiting Hedgehog pathway.


2012 ◽  
Vol 65 (3-4) ◽  
pp. 152-157
Author(s):  
Snezana Tesic-Rajkovic ◽  
Biljana Radovanovic-Dinic ◽  
Tatjana Jevtovic-Stoimenov

Introduction. Alcoholic acute pancreatitis occurs in 10% of alcoholics, who take more than 80g alcohol daily. Different biochemical markers are used to diagnose acute pancreatitis, and some of them may help in establishing etiology of acute pancreatitis. Material and Methods. This study is a prospective review of 21 patients. All patients were hospitalized at the Department for Gastroenterology and Hepatology or at the Department for Surgery of the Clinical Centre of Nis in the period from August 1st 2009 to March 1st 2010 with diagnosis of acute alcoholic pancreatitis. Detailed anamnesis, clinical examination, biochemical analyses and ultrasonography of the upper abdomen were done in all patients. All patients provided data on alcohol abuse. Results. The analysis of the corresponding biochemical parameters revealed a statistically significant correlation between the following values: serum amylase and serum lipase (R=0.964674; p<0.001), cholesterol and triglycerides (R=0.93789; p<0.001), total and direct bilirubin (R=0.857899; p<0.001) and between aspartate aminotransferase and alanine aminotransferase (R=0.824461, p<0.001) in patients with alcoholic acute pancreatitis. In addition, there was a statistically significant correlation between the values of serum amylase and urinary amylase (R=0.582742, p<0.001). Discussion. The analysis of biochemical markers showed that some of them were significant for beforehand diagnosis of alcoholic acute pancreatitis, which is in accordance with other studies. Conclusion Some biochemical parameters can be potential predictors of alcoholic acute pancreatitis (lipase/amylase ratio >2, greater ratio of aspartate aminotransferase/ alanine aminotransferase, enhanced triglycerides and values of mean corpuscular volume.


2013 ◽  
Vol 24 (6) ◽  
pp. 571-577 ◽  
Author(s):  
Sanjay Swaminathan ◽  
Lue Dai ◽  
H. Clifford Lane ◽  
Tomozumi Imamichi

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2659 ◽  
Author(s):  
Sergej M. Ostojic

Molecular hydrogen (H2) has recently been recognized as a potential novel therapeutic agent in biomedicine. Initially proposed to be a possible treatment for certain types of neuromuscular disorders, cardio-metabolic diseases and cancer, H2 improved clinical end-points and surrogate markers in several clinical trials, mainly acting as an anti-inflammatory agent and powerful antioxidant. In this paper, the medicinal properties of H2 in musculoskeletal medicine are discussed with the aim to provide an updated and practical overview for health professionals working in this field.


PLoS ONE ◽  
2012 ◽  
Vol 7 (2) ◽  
pp. e32521 ◽  
Author(s):  
Abhay kumar Singh ◽  
Ratnakar Singh ◽  
Farhat Naz ◽  
Shyam Singh Chauhan ◽  
Amit Dinda ◽  
...  

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