scholarly journals CTRP3 ameliorates cerulein-induced severe acute pancreatitis in mice via SIRT1/NF-κB/p53 axis

2020 ◽  
Vol 40 (10) ◽  
Author(s):  
Chunyang Lv ◽  
Yuan He ◽  
Mingli Wei ◽  
Guiyun Xu ◽  
Chuang Chen ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Mouse Models ◽  
Severe Acute Pancreatitis ◽  
Intraperitoneal Injection ◽  
Protective Effects ◽  
P53 Signaling ◽  
Abdominal Disease ◽  
Life Threatening ◽  
Dependent Protein

Abstract Severe acute pancreatitis (SAP) is a common and life-threatening clinical acute abdominal disease. C1q/tumor necrosis factor-related protein 3 (CTRP3), a novel paralog of adiponectin, has been identified as a crucial regulator in multiple types of inflammatory disorders. However, the biological role of CTRP3 in SAP remains poorly understood. The present study aimed to characterize the role of CTRP3 in SAP and illuminate the potential mechanisms involved. In the current study, SAP mouse models were induced by seven hourly intraperitoneal injection of cerulein (50 μg/kg) and an immediate intraperitoneal injection of lipopolysaccharide (10 mg/kg) after the last cerulein administration. Histological examination and serological analysis demonstrated that SAP mouse models were successfully established. Herein, we found that CTRP3 expression was significantly decreased in the pancreatic tissues of SAP mice compared with normal control mice. Furthermore, we explored the effects of CTRP3 rescue in SAP mice and discovered that CTRP3 overexpression attenuated pathological lesions, inhibited inflammatory mediator release and repressed acinar cell apoptosis. Notably, mechanistic studies revealed that CTRP3 overexpression suppressed NF-κB p65 phosphorylation and p53 acetylation to alleviate cerulein-induced SAP in mouse models through activation of silent information regulator 1 (SIRT1), a nicotinamide adenine dinucleotide-dependent protein deacetylase. Collectively, our data indicate that CTRP3 may exert its protective effects in SAP mice via regulation of SIRT1-mediated NF-κB and p53 signaling pathways, implying a promising therapeutic strategy against SAP.

scholarly journals Treatment of Severe Acute Pancreatitis and Related Lung Injury by Targeting Gasdermin D-Mediated Pyroptosis

2021 ◽  
Vol 9 ◽  
Author(s):  
Jinxiang Wu ◽  
Jintao Zhang ◽  
Jiping Zhao ◽  
Shihong Chen ◽  
Tao Zhou ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Lung Injury ◽  
Mouse Models ◽  
Severe Acute Pancreatitis ◽  
Proinflammatory Cytokines ◽  
Potential Application ◽  
Receptor Protein ◽  
Wild Type ◽  
Functional Relevance

The functional relevance and effects of the pyroptosis executioner gasdermin D (GSDMD) on severe acute pancreatitis (SAP)-associated lung injury are unclear. We established caerulein-induced mouse models of SAP-associated lung injury, which showed that GSDMD-mediated pyroptosis was activated in both pancreatic and lung tissues. Compared with Gsdmd wild-type SAP mouse models, Gsdmd knockout (Gsdmd–/–) ameliorated SAP-induced pancreas and related lung injury. Additionally, we investigated the effects of disulfiram on the treatment of SAP. Disulfiram is a Food and Drug Administration (FDA)-approved anti-alcoholism drug, which is reported as an effective pyroptosis inhibitor by either directly covalently modifying GSDMD or indirectly inhibiting the cleavage of GSDMD via inactivating Nod-like receptor protein 3 inflammasome. We demonstrated that disulfiram inhibited the cleavage of GSDMD, alleviated caerulein-induced SAP and related lung injury, and decreased the expression levels of proinflammatory cytokines (IL-1β and IL-18). Collectively, these findings disclosed the role of GSDMD-mediated pyroptosis in SAP and the potential application of disulfiram in the treatment of SAP.

Severe acute pancreatitis- it's diagnosis and management- A study of 20 cases

2019 ◽  
Vol 8 (2) ◽  
pp. 17-29
Author(s):  
Mohammad Monir Hossain ◽  
S M Shakwat Hossain ◽  
Delowar Hossain
Keyword(s):  
Acute Pancreatitis ◽  
Conservative Treatment ◽  
Severe Acute Pancreatitis ◽  
Pancreatic Necrosis ◽  
Military Hospital ◽  
Fatty Tissue ◽  
Ct Findings ◽  
Contrast Enhanced Ct ◽  
Management Protocol ◽  
Life Threatening

Background: Severe acute pancreatitis is defined as pancreatitis in which there is persistent organ failure that does not resolve within 48 hours. Severe acute Pancreatitis is characterized by pancreatic necrosis, a severe systemic inflammatory response and often multiorgan failure. Severe acute pancreatitis is a serious and life threatening disease. Mortality varies from 20 to 50 percent. Objective: The objectives of this study are to develop our knowledge about presentation and diagnosis of severe acute pancreatitis, and to develop a standard management protocol to rescue that patient suffering from severe acute pancreatitis. Methods: This observational study was carried out in Combined Military Hospital (CMH) Dhaka, during the period of August 2014 - Feb 2015. A total 20 patients of severe acute pancreatitis were studied prospectively, evaluated and managed. Results: In this study, out of 20 patients 12(60%) male and 08(40%) female. Male: Female = 3:2. The youngest patient of this series was 03 years and oldest was of 55 years. First categorization of severity of acute pancreatitis was done on the basis of Ranson score. Those patients whose score is 3 or more are categorized as severe. After categorization subsequent management was planned on the basis of laboratory and CT findings. Out of 20 patients all have raised WBC, serum Calcium level decrease in 16 patients, LDH raised in 16 patients, PaO2 decrease in 14 patients, Base deficitincreased in 12 patients, and blood urea nitrate raised in 14 patients. Contrast enhanced CT scan done in all patients and 12 patients were found with reduced enhancement in pancreas, peripancreatic edema and stranding of fatty tissue and remaining 8 patients have fluid collected in peri- and retro pancreatic space. Total 12 patients were given conservative treatment. Remaining 8 patients were operated whose CT findings were reduced enhancement in pancreas and these patients were suspected for infective pancreatic necrosis. In this study 3 patients were expired. Out of these three patients, 2 patients underwent operative intervention and 1 patient was given conservative treatment. Conclusion: Severe acute pancreatitis is a life threatening condition. Its serious regional and systemic involvement causes multiple organ or system failure. Early diagnosis and effective treatment can significantly reduce the mortality and morbidity. CBMJ 2019 July: Vol. 08 No. 02 P: 17-29

scholarly journals Role of CARD9 in inflammatory signal pathway of peritoneal macrophages in severe acute pancreatitis

2020 ◽  
Vol 24 (17) ◽  
pp. 9774-9785
Author(s):  
Jing Wang ◽  
Jun Tian ◽  
Yang‐huan He ◽  
Zhi‐wen Yang ◽  
Lin Wang ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Severe Acute Pancreatitis ◽  
Peritoneal Macrophages ◽  
Signal Pathway

scholarly journals Targeting neutrophil extracellular traps in severe acute pancreatitis treatment

2020 ◽  
Vol 13 ◽  
pp. 175628482097491
Author(s):  
Jing Hu ◽  
Hongxin Kang ◽  
Huan Chen ◽  
Jiaqi Yao ◽  
Xiaolin Yi ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Severe Acute Pancreatitis ◽  
Inflammatory Cells ◽  
Neutrophil Extracellular Traps ◽  
Multiple Organ ◽  
Organ Injury ◽  
Normal Tissues ◽  
Pathogen Invasion ◽  
Extracellular Traps ◽  
Abdominal Disease

Severe acute pancreatitis (SAP) is a critical abdominal disease associated with high death rates. A systemic inflammatory response promotes disease progression, resulting in multiple organ dysfunction. The functions of neutrophils in the pathology of SAP have been presumed traditionally to be activation of chemokine and cytokine cascades accompanying the inflammatory process. Recently, since their discovery, a new type of antimicrobial mechanism, neutrophil extracellular traps (NETs), and their role in SAP, has attracted widespread attention from the scientific community. Significantly different from phagocytosis and degranulation, NETs kill extracellular microorganisms by releasing DNA fibers decorated with granular proteins. In addition to their strong antimicrobial functions, NETs participate in the pathophysiological process of many noninfectious diseases. In SAP, NETs injure normal tissues under inflammatory stress, which is associated with the activation of inflammatory cells, to cause an inflammatory cascade, and SAP products also trigger NET formation. Thus, due to the interaction between NET generation and SAP, a treatment targeting NETs might become a key point in SAP therapy. In this review, we summarize the mechanism of NETs in protecting the host from pathogen invasion, the stimulus that triggers NET formation, organ injury associated with SAP involving NETs, methods to interrupt the harmful effects of NETs, and different therapeutic strategies to preserve the organ function of patients with SAP by targeting NETs.

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